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image of Impact and Significance of Viral Vectors for siRNA Delivery in the Treatment of Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) remains a major challenge in developing effective treatments due to its complex pathophysiology, including the accumulation of amyloid-beta plaques and tau tangles. Small interfering RNA (siRNA) technology offers promise for targeted gene silencing, but effective delivery to the central nervous system remains a significant obstacle. Viral vectors have emerged as potent delivery vehicles for transporting siRNA to neural tissues. This review explores the utilization of viral vectors for siRNA delivery in AD, focusing on delivery strategies and challenges. We discuss the design and optimization of viral vectors, targeting strategies, and safety considerations. Additionally, we examine recent advancements and prospects for enhancing viral vector-mediated siRNA delivery in AD.

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2025-01-09
2025-03-26

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References

  1. Zvěřová M. Clinical aspects of Alzheimer’s disease. Clin. Biochem. 2019 72 3 6 10.1016/j.clinbiochem.2019.04.015 31034802
    [Google Scholar]
  2. Feldman H.H. Woodward M. The staging and assessment of moderate to severe Alzheimer disease. Neurology 2005 65 6_suppl_3 Suppl. 3 S10 S7 10.1212/WNL.65.6_suppl_3.S10
    [Google Scholar]
  3. Sperling R.A. Aisen P.S. Beckett L.A. Bennett D.A. Craft S. Fagan A.M. Iwatsubo T. Jack C.R. Jr Kaye J. Montine T.J. Park D.C. Reiman E.M. Rowe C.C. Siemers E. Stern Y. Yaffe K. Carrillo M.C. Thies B. Morrison-Bogorad M. Wagster M.V. Phelps C.H. Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the National Institute on Aging‐Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011 7 3 280 292 10.1016/j.jalz.2011.03.003 21514248
    [Google Scholar]
  4. Sadigh-Eteghad S. Sabermarouf B. Majdi A. Talebi M. Farhoudi M. Mahmoudi J. Amyloid-beta: a crucial factor in Alzheimer’s disease. Med. Princ. Pract. 2015 24 1 1 10 10.1159/000369101 25471398
    [Google Scholar]
  5. Huang H.C. Jiang Z.F. Accumulated amyloid-β peptide and hyperphosphorylated tau protein: relationship and links in Alzheimer’s disease. J. Alzheimers Dis. 2009 16 1 15 27 10.3233/JAD‑2009‑0960 19158417
    [Google Scholar]
  6. Penke B. Bogár F. Fülöp L. β-Amyloid and the pathomechanisms of Alzheimer’s disease: a comprehensive view. Molecules 2017 22 10 1692 10.3390/molecules22101692 28994715
    [Google Scholar]
  7. Tu S. Okamoto S. Lipton S.A. Xu H. Oligomeric Aβ-induced synaptic dysfunction in Alzheimer’s disease. Mol. Neurodegener. 2014 9 1 48 10.1186/1750‑1326‑9‑48 25394486
    [Google Scholar]
  8. Avila-Muñoz E. Arias C. When astrocytes become harmful: Functional and inflammatory responses that contribute to Alzheimer’s disease. Ageing Res. Rev. 2014 18 29 40 10.1016/j.arr.2014.07.004 25078115
    [Google Scholar]
  9. Kempuraj D. Thangavel R. Natteru P.A. Selvakumar G.P. Saeed D. Zahoor H. Neuroinflammation induces neurodegeneration. J. Neurol. Neurosurg. Spine. 2016 1 1 1003
    [Google Scholar]
  10. Aslan M. Ozben T. Reactive oxygen and nitrogen species in Alzheimer’s disease. Curr. Alzheimer Res. 2004 1 2 111 119 10.2174/1567205043332162 15975075
    [Google Scholar]
  11. Cha M.Y. Han S.H. Son S.M. Hong H.S. Choi Y.J. Byun J. Mook-Jung I. Mitochondria-specific accumulation of amyloid β induces mitochondrial dysfunction leading to apoptotic cell death. PLoS One 2012 7 4 e34929 10.1371/journal.pone.0034929 22514691
    [Google Scholar]
  12. Alonso A.C. Grundke-Iqbal I. Iqbal K. Alzheimer’s disease hyperphosphorylated tau sequesters normal tau into tangles of filaments and disassembles microtubules. Nat. Med. 1996 2 7 783 787 10.1038/nm0796‑783 8673924
    [Google Scholar]
  13. Gomez-Isla T. Spires T. De Calignon A. Hyman B.T. Neuropathology of Alzheimer’s disease. Handb. Clin. Neurol. 2008 89 233 243 10.1016/S0072‑9752(07)01222‑5 18631748
    [Google Scholar]
  14. Stokin G.B. Goldstein L.S.B. Axonal transport and Alzheimer’s disease. Annu. Rev. Biochem. 2006 75 1 607 627 10.1146/annurev.biochem.75.103004.142637 16756504
    [Google Scholar]
  15. Siano G. Falcicchia C. Origlia N. Cattaneo A. Di Primio C. Non-canonical roles of tau and their contribution to synaptic dysfunction. Int. J. Mol. Sci. 2021 22 18 10145 10.3390/ijms221810145 34576308
    [Google Scholar]
  16. Chen X.Q. Mobley W.C. Alzheimer disease pathogenesis: insights from molecular and cellular biology studies of oligomeric Aβ and tau species. Front. Neurosci. 2019 13 659 10.3389/fnins.2019.00659 31293377
    [Google Scholar]
  17. Rajmohan R. Reddy P.H. Amyloid-beta and phosphorylated tau accumulations cause abnormalities at synapses of Alzheimer’s disease neurons. J. Alzheimers Dis. 2017 57 4 975 999 10.3233/JAD‑160612 27567878
    [Google Scholar]
  18. Bhatia V. Sharma S. Role of mitochondrial dysfunction, oxidative stress and autophagy in progression of Alzheimer’s disease. J. Neurol. Sci. 2021 421 117253 10.1016/j.jns.2020.117253 33476985
    [Google Scholar]
  19. Zhao Y. Zhao B. Oxidative stress and the pathogenesis of Alzheimer's disease. Oxid Med Cell Longev. 2013 2013 316523 10.1155/2013/316523
    [Google Scholar]
  20. Takuma K. Yan S.S. Stern D.M. Yamada K. Mitochondrial dysfunction, endoplasmic reticulum stress, and apoptosis in Alzheimer’s disease. J. Pharmacol. Sci. 2005 97 3 312 316 10.1254/jphs.CPJ04006X 15750290
    [Google Scholar]
  21. Cummings J. New approaches to symptomatic treatments for Alzheimer’s disease. Mol. Neurodegener. 2021 16 1 13
    [Google Scholar]
  22. Chen L. Cruz E. Oikari L.E. Padmanabhan P. Song J. Götz J. Opportunities and challenges in delivering biologics for Alzheimer’s disease by low-intensity ultrasound. Adv. Drug Deliv. Rev. 2022 189 114517 10.1016/j.addr.2022.114517 36030018
    [Google Scholar]
  23. Luissint A.C. Artus C. Glacial F. Ganeshamoorthy K. Couraud P.O. Tight junctions at the blood brain barrier: physiological architecture and disease-associated dysregulation. Fluids Barriers CNS 2012 9 1 23 10.1186/2045‑8118‑9‑23 23140302
    [Google Scholar]
  24. Bors L.A. Erdő F. Overcoming the blood–brain barrier. challenges and tricks for CNS drug delivery. Sci. Pharm. 2019 87 1 6 10.3390/scipharm87010006
    [Google Scholar]
  25. Wong K.H. Riaz M.K. Xie Y. Zhang X. Liu Q. Chen H. Bian Z. Chen X. Lu A. Yang Z. Review of current strategies for delivering Alzheimer’s disease drugs across the blood-brain barrier. Int. J. Mol. Sci. 2019 20 2 381 10.3390/ijms20020381 30658419
    [Google Scholar]
  26. Jakob-Roetne R. Jacobsen H. Alzheimer’s disease: from pathology to therapeutic approaches. Angew. Chem. Int. Ed. 2009 48 17 3030 3059 10.1002/anie.200802808 19330877
    [Google Scholar]
  27. Teixeira M.I. Lopes C.M. Amaral M.H. Costa P.C. Current insights on lipid nanocarrier-assisted drug delivery in the treatment of neurodegenerative diseases. Eur. J. Pharm. Biopharm. 2020 149 192 217 10.1016/j.ejpb.2020.01.005 31982574
    [Google Scholar]
  28. Mendonça M.C.P. Kont A. Aburto M.R. Cryan J.F. O’Driscoll C.M. Advances in the design of (nano) formulations for delivery of antisense oligonucleotides and small interfering RNA: Focus on the central nervous system. Mol. Pharm. 2021 18 4 1491 1506 10.1021/acs.molpharmaceut.0c01238 33734715
    [Google Scholar]
  29. Mitchell M.J. Billingsley M.M. Haley R.M. Wechsler M.E. Peppas N.A. Langer R. Engineering precision nanoparticles for drug delivery. Nat. Rev. Drug Discov. 2021 20 2 101 124 10.1038/s41573‑020‑0090‑8 33277608
    [Google Scholar]
  30. Kimura S. Harashima H. Current status and challenges associated with CNS-targeted gene delivery across the BBB. Pharmaceutics 2020 12 12 1216 10.3390/pharmaceutics12121216 33334049
    [Google Scholar]
  31. Hong C-S. Goins W.F. Goss J.R. Burton E.A. Glorioso J.C. Herpes simplex virus RNAi and neprilysin gene transfer vectors reduce accumulation of Alzheimer’s disease-related amyloid-β peptide in vivo. Gene Ther. 2006 13 14 1068 1079 10.1038/sj.gt.3302719 16541122
    [Google Scholar]
  32. Raikwar S.P. Thangavel R. Dubova I. Selvakumar G.P. Ahmed M.E. Kempuraj D. Zaheer S.A. Iyer S.S. Zaheer A. Targeted gene editing of glia maturation factor in microglia: a novel Alzheimer’s disease therapeutic target. Mol. Neurobiol. 2019 56 1 378 393 10.1007/s12035‑018‑1068‑y 29704201
    [Google Scholar]
  33. Dana H. Chalbatani G.M. Mahmoodzadeh H. Gharagouzlo E. Karimloo R. Rezaiean O. Moradzadeh A. Mazraeh A. Marmari V. Rashno M.M. Mehmandoost N. Moazzen F. Ebrahimi M. Abadi S.J. Molecular mechanisms and biological functions of siRNA. Int. J. Biomed. Sci. 2017 13 2 48 57 10.59566/IJBS.2017.13048 28824341
    [Google Scholar]
  34. Lin X. Ruan X. Anderson M.G. McDowell J.A. Kroeger P.E. Fesik S.W. Shen Y. siRNA-mediated off-target gene silencing triggered by a 7 nt complementation. Nucleic Acids Res. 2005 33 14 4527 4535 10.1093/nar/gki762 16091630
    [Google Scholar]
  35. Imran Sajid M. Sultan Sheikh F. Anis F. Nasim N. Sumbria R.K. Nauli S.M. Kumar Tiwari R. siRNA drug delivery across the blood–brain barrier in Alzheimer’s disease. Adv. Drug Deliv. Rev. 2023 199 114968 10.1016/j.addr.2023.114968 37353152
    [Google Scholar]
  36. Ohno M. Alzheimer’s therapy targeting the β-secretase enzyme BACE1: Benefits and potential limitations from the perspective of animal model studies. Brain Res. Bull. 2016 126 Pt 2 183 198 10.1016/j.brainresbull.2016.04.007 27093940
    [Google Scholar]
  37. Wang P. Zheng X. Guo Q. Yang P. Pang X. Qian K. Lu W. Zhang Q. Jiang X. Systemic delivery of BACE1 siRNA through neuron-targeted nanocomplexes for treatment of Alzheimer’s disease. J. Control. Release 2018 279 220 233 10.1016/j.jconrel.2018.04.034 29679667
    [Google Scholar]
  38. Congdon E.E. Sigurdsson E.M. Tau-targeting therapies for Alzheimer disease. Nat. Rev. Neurol. 2018 14 7 399 415 10.1038/s41582‑018‑0013‑z 29895964
    [Google Scholar]
  39. Iqbal K. Liu F. Gong C.X. Grundke-Iqbal I. Tau in Alzheimer disease and related tauopathies. Curr. Alzheimer Res. 2010 7 8 656 664 10.2174/156720510793611592 20678074
    [Google Scholar]
  40. Zhang C.C. Xing A. Tan M.S. Tan L. Yu J.T. The role of MAPT in neurodegenerative diseases: genetics, mechanisms and therapy. Mol. Neurobiol. 2016 53 7 4893 4904 10.1007/s12035‑015‑9415‑8 26363795
    [Google Scholar]
  41. Balaji V. Kaniyappan S. Mandelkow E. Wang Y. Mandelkow E.M. Pathological missorting of endogenous MAPT/Tau in neurons caused by failure of protein degradation systems. Autophagy 2018 14 12 15548627.2018.1509607 10.1080/15548627.2018.1509607 30145931
    [Google Scholar]
  42. Solito E. Sastre M. Microglia function in Alzheimer’s disease. Front. Pharmacol. 2012 3 14 10.3389/fphar.2012.00014 22363284
    [Google Scholar]
  43. Li X. Zhang F. Targeting TREM2 for Parkinson’s disease: where to go? Front. Immunol. 2021 12 795036 10.3389/fimmu.2021.795036 35003116
    [Google Scholar]
  44. Griciuc A. Federico A.N. Natasan J. Forte A.M. McGinty D. Nguyen H. Volak A. LeRoy S. Gandhi S. Lerner E.P. Hudry E. Tanzi R.E. Maguire C.A. Gene therapy for Alzheimer’s disease targeting CD33 reduces amyloid beta accumulation and neuroinflammation. Hum. Mol. Genet. 2020 29 17 2920 2935 10.1093/hmg/ddaa179 32803224
    [Google Scholar]
  45. Liu W. Taso O. Wang R. Bayram S. Graham A.C. Garcia-Reitboeck P. Mallach A. Andrews W.D. Piers T.M. Botia J.A. Pocock J.M. Cummings D.M. Hardy J. Edwards F.A. Salih D.A. Trem2 promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions. Hum. Mol. Genet. 2020 29 19 3224 3248 10.1093/hmg/ddaa209 32959884
    [Google Scholar]
  46. Safieh M. Korczyn A.D. Michaelson D.M. ApoE4: an emerging therapeutic target for Alzheimer’s disease. BMC Med. 2019 17 1 64 10.1186/s12916‑019‑1299‑4 30890171
    [Google Scholar]
  47. Yamazaki Y. Zhao N. Caulfield T.R. Liu C.C. Bu G. Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies. Nat. Rev. Neurol. 2019 15 9 501 518 10.1038/s41582‑019‑0228‑7 31367008
    [Google Scholar]
  48. Eskandari-Sedighi G. Jung J. Macauley M.S. CD33 isoforms in microglia and Alzheimer’s disease: Friend and foe. Mol. Aspects Med. 2023 90 101111 10.1016/j.mam.2022.101111 35940942
    [Google Scholar]
  49. Whitehead K.A. Langer R. Anderson D.G. Knocking down barriers: advances in siRNA delivery. Nat. Rev. Drug Discov. 2009 8 2 129 138 10.1038/nrd2742 19180106
    [Google Scholar]
  50. dos Santos Rodrigues B. Lakkadwala S. Kanekiyo T. Singh J. Development and screening of brain-targeted lipid-based nanoparticles with enhanced cell penetration and gene delivery properties. Int. J. Nanomedicine 2019 14 6497 6517 10.2147/IJN.S215941 31616141
    [Google Scholar]
  51. Whitehead K.A. Dahlman J.E. Langer R.S. Anderson D.G. Silencing or stimulation? siRNA delivery and the immune system. Annu. Rev. Chem. Biomol. Eng. 2011 2 1 77 96 10.1146/annurev‑chembioeng‑061010‑114133 22432611
    [Google Scholar]
  52. Chen S.H. Zhaori G. Potential clinical applications of siRNA technique: benefits and limitations. Eur. J. Clin. Invest. 2011 41 2 221 232 10.1111/j.1365‑2362.2010.02400.x 20964680
    [Google Scholar]
  53. Scaggiante B. Dapas B. Farra R. Grassi M. Pozzato G. Giansante C. Grassi G. Grassi G. Improving siRNA bio-distribution and minimizing side effects. Curr. Drug Metab. 2011 12 1 11 23 10.2174/138920011794520017 21222588
    [Google Scholar]
  54. Shum K. Rossi J. SiRNA delivery methods. Methods in Molecular Biology. Springer 2016 10.1007/978‑1‑4939‑3112‑5
    [Google Scholar]
  55. Yuan X. Naguib S. Wu Z. Recent advances of siRNA delivery by nanoparticles. Expert Opin. Drug Deliv. 2011 8 4 521 536 10.1517/17425247.2011.559223 21413903
    [Google Scholar]
  56. Aundhia C. Shah N. Talele C. Zanwar A. Kumari M. Patil S. Enhancing Gene Therapy through Ultradeformable Vesicles for Efficient siRNA Delivery. Pharm. Nanotechnol. 2024 38284710
    [Google Scholar]
  57. Marquez A.R. Madu C.O. Lu Y. An overview of various carriers for siRNA delivery. Oncomedicine 2018 3 48 58 10.7150/oncm.25785
    [Google Scholar]
  58. Yuan B. Zhao Y. Dong S. Sun Y. Hao F. Xie J. Teng L. Lee R.J. Fu Y. Bi Y. Cell-penetrating peptide-coated liposomes for drug delivery across the blood–brain barrier. Anticancer Res. 2019 39 1 237 243 10.21873/anticanres.13103 30591464
    [Google Scholar]
  59. Gao H. Zhang Q. Yu Z. He Q. Cell-penetrating peptide-based intelligent liposomal systems for enhanced drug delivery. Curr. Pharm. Biotechnol. 2014 15 3 210 219 10.2174/1389201015666140617092552 24938896
    [Google Scholar]
  60. Zu H. Gao D. Non-viral vectors in gene therapy: recent development, challenges, and prospects. AAPS J. 2021 23 4 78 10.1208/s12248‑021‑00608‑7 34076797
    [Google Scholar]
  61. Warnock J.N. Daigre C. Al-Rubeai M. Introduction to viral vectors. Viral vectors for gene therapy: methods and protocols Springer 2011 10.1007/978‑1‑61779‑095‑9_1
    [Google Scholar]
  62. Rao D.D. Vorhies J.S. Senzer N. Nemunaitis J. siRNA vs. shRNA: Similarities and differences. Adv. Drug Deliv. Rev. 2009 61 9 746 759 10.1016/j.addr.2009.04.004 19389436
    [Google Scholar]
  63. Cabianca D.S. Gabellini D. Alternative pre-mRNA Splicing: Theory and Protocols Alternative pre-mRNA Splicing Wiley-VCH Verlag GmbH & Co. KGaA 2012 10.1002/9783527636778
    [Google Scholar]
  64. Singh S. Narang A.S. Mahato R.I. Subcellular Fate and Off-Target Effects of siRNA, shRNA, and miRNA. Pharm. Res. 2011 28 12 2996 3015 10.1007/s11095‑011‑0608‑1 22033880
    [Google Scholar]
  65. White E. Schlackow M. Kamieniarz-Gdula K. Proudfoot N.J. Gullerova M. Human nuclear Dicer restricts the deleterious accumulation of endogenous double-stranded RNA. Nat. Struct. Mol. Biol. 2014 21 6 552 559 10.1038/nsmb.2827 24814348
    [Google Scholar]
  66. Vannucci L. Lai M. Chiuppesi F. Ceccherini-Nelli L. Pistello M. Viral vectors: a look back and ahead on gene transfer technology. New Microbiol. 2013 36 1 1 22 23435812
    [Google Scholar]
  67. Conniot J. Talebian S. Simões S. Ferreira L. Conde J. Revisiting gene delivery to the brain: silencing and editing. Biomater. Sci. 2021 9 4 1065 1087 10.1039/D0BM01278E 33315025
    [Google Scholar]
  68. Krishnan N. Peng F.X. Mohapatra A. Fang R.H. Zhang L. Genetically engineered cellular nanoparticles for biomedical applications. Biomaterials 2023 296 122065 10.1016/j.biomaterials.2023.122065 36841215
    [Google Scholar]
  69. Ahmed T. Lipid nanoparticle mediated small interfering RNA delivery as a potential therapy for Alzheimer’s disease. Eur. J. Neurosci. 2024 59 11 2915 2954 10.1111/ejn.16336 38622050
    [Google Scholar]
  70. Kwon I. Schaffer D.V. Designer gene delivery vectors: molecular engineering and evolution of adeno-associated viral vectors for enhanced gene transfer. Pharm. Res. 2008 25 3 489 499 10.1007/s11095‑007‑9431‑0 17763830
    [Google Scholar]
  71. Nicklin S. Baker A. Tropism-modified adenoviral and adeno-associated viral vectors for gene therapy. Curr. Gene Ther. 2002 2 3 273 293 10.2174/1566523023347797 12189716
    [Google Scholar]
  72. Mani S. Jindal D. Singh M. Gene therapy, a potential therapeutic tool for neurological and neuropsychiatric disorders: applications, challenges and future perspective. Curr. Gene Ther. 2023 23 1 20 40 10.2174/1566523222666220328142427 35345999
    [Google Scholar]
  73. Yin H. Kanasty R.L. Eltoukhy A.A. Vegas A.J. Dorkin J.R. Anderson D.G. Non-viral vectors for gene-based therapy. Nat. Rev. Genet. 2014 15 8 541 555 10.1038/nrg3763 25022906
    [Google Scholar]
  74. Zinn E. Vandenberghe L.H. Adeno-associated virus: fit to serve. Curr. Opin. Virol. 2014 8 90 97 10.1016/j.coviro.2014.07.008 25128609
    [Google Scholar]
  75. Mingozzi F. High K.A. Immune responses to AAV in clinical trials. Curr. Gene Ther. 2011 11 4 321 330 10.2174/156652311796150354 21557723
    [Google Scholar]
  76. Muhuri M. Levy D.I. Schulz M. McCarty D. Gao G. Durability of transgene expression after rAAV gene therapy. Mol. Ther. 2022 30 4 1364 1380 10.1016/j.ymthe.2022.03.004 35283274
    [Google Scholar]
  77. Gil-Farina I. Schmidt M. Interaction of vectors and parental viruses with the host genome. Curr. Opin. Virol. 2016 21 35 40 10.1016/j.coviro.2016.07.004 27474966
    [Google Scholar]
  78. Wanisch K. Yáñez-Muñoz R.J. Integration-deficient lentiviral vectors: a slow coming of age. Mol. Ther. 2009 17 8 1316 1332 10.1038/mt.2009.122 19491821
    [Google Scholar]
  79. Gurumoorthy N. Nordin F. Tye G.J. Wan Kamarul Zaman W.S. Ng M.H. Non-integrating lentiviral vectors in clinical applications: A glance through. Biomedicines 2022 10 1 107 10.3390/biomedicines10010107 35052787
    [Google Scholar]
  80. Mijanović O. Branković A. Borovjagin A.V. Butnaru D.V. Bezrukov E.A. Sukhanov R.B. Shpichka A. Timashev P. Ulasov I. Battling neurodegenerative diseases with adeno-associated virus-based approaches. Viruses 2020 12 4 460 10.3390/v12040460 32325732
    [Google Scholar]
  81. Perez B.A. Shutterly A. Chan Y.K. Byrne B.J. Corti M. Management of neuroinflammatory responses to AAV-mediated gene therapies for neurodegenerative diseases. Brain Sci. 2020 10 2 119 10.3390/brainsci10020119 32098339
    [Google Scholar]
  82. Hinderer C. Bell P. Vite C.H. Louboutin J.P. Grant R. Bote E. Yu H. Pukenas B. Hurst R. Wilson J.M. Widespread gene transfer in the central nervous system of cynomolgus macaques following delivery of AAV9 into the cisterna magna. Mol. Ther. Methods Clin. Dev. 2014 1 14051 10.1038/mtm.2014.51 26052519
    [Google Scholar]
  83. Maguire C.A. Ramirez S.H. Merkel S.F. Sena-Esteves M. Breakefield X.O. Gene therapy for the nervous system: challenges and new strategies. Neurotherapeutics 2014 11 4 817 839 10.1007/s13311‑014‑0299‑5 25159276
    [Google Scholar]
  84. Wu Z. Yang H. Colosi P. Effect of genome size on AAV vector packaging. Mol. Ther. 2010 18 1 80 86 10.1038/mt.2009.255 19904234
    [Google Scholar]
  85. Whitehead M. Osborne A. Yu-Wai-Man P. Martin K. Humoral immune responses to AAV gene therapy in the ocular compartment. Biol. Rev. Camb. Philos. Soc. 2021 96 4 1616 1644 10.1111/brv.12718 33837614
    [Google Scholar]
  86. Gorbatyuk M. Justilien V. Liu J. Hauswirth W.W. Lewin A.S. Suppression of mouse rhodopsin expression in vivo by AAV mediated siRNA delivery. Vision Res. 2007 47 9 1202 1208 10.1016/j.visres.2006.11.026 17292939
    [Google Scholar]
  87. Guo Q. Zheng X. Yang P. Pang X. Qian K. Wang P. Xu S. Sheng D. Wang L. Cao J. Lu W. Zhang Q. Jiang X. Small interfering RNA delivery to the neurons near the amyloid plaques for improved treatment of Alzheimer׳s disease. Acta Pharm. Sin. B 2019 9 3 590 603 10.1016/j.apsb.2018.12.010 31193846
    [Google Scholar]
  88. Zhang C. Yao T. Zheng Y. Li Z. Zhang Q. Zhang L. Zhou D. Development of next generation adeno-associated viral vectors capable of selective tropism and efficient gene delivery. Biomaterials 2016 80 134 145 10.1016/j.biomaterials.2015.11.066 26708090
    [Google Scholar]
  89. Munis A.M. Gene therapy applications of non-human lentiviral vectors. Viruses 2020 12 10 1106 10.3390/v12101106 33003635
    [Google Scholar]
  90. Vargas J.E. Chicaybam L. Stein R.T. Tanuri A. Delgado-Cañedo A. Bonamino M.H. Retroviral vectors and transposons for stable gene therapy: advances, current challenges and perspectives. J. Transl. Med. 2016 14 1 288 10.1186/s12967‑016‑1047‑x 27729044
    [Google Scholar]
  91. Escors D. Breckpot K. Lentiviral vectors in gene therapy: their current status and future potential. Arch. Immunol. Ther. Exp. (Warsz.) 2010 58 2 107 119 10.1007/s00005‑010‑0063‑4 20143172
    [Google Scholar]
  92. Vodicka M.A. Determinants for lentiviral infection of non-dividing cells. Somat. Cell Mol. Genet. 2001 26 1/6 35 49 10.1023/A:1021022629126 12465461
    [Google Scholar]
  93. Kanninen K. Heikkinen R. Malm T. Rolova T. Kuhmonen S. Leinonen H. Ylä-Herttuala S. Tanila H. Levonen A.L. Koistinaho M. Koistinaho J. Intrahippocampal injection of a lentiviral vector expressing Nrf2 improves spatial learning in a mouse model of Alzheimer’s disease. Proc. Natl. Acad. Sci. USA 2009 106 38 16505 16510 10.1073/pnas.0908397106 19805328
    [Google Scholar]
  94. Zhang W. Zhao H. Wu Q. Xu W. Xia M. Knockdown of BACE1‑AS by siRNA improves memory and learning behaviors in Alzheimer’s disease animal model. Exp. Ther. Med. 2018 16 3 2080 2086 10.3892/etm.2018.6359 30186443
    [Google Scholar]
  95. Singer O. Marr R.A. Rockenstein E. Crews L. Coufal N.G. Gage F.H. Verma I.M. Masliah E. Targeting BACE1 with siRNAs ameliorates Alzheimer disease neuropathology in a transgenic model. Nat. Neurosci. 2005 8 10 1343 1349 10.1038/nn1531 16136043
    [Google Scholar]
  96. Sanber K.S. Knight S.B. Stephen S.L. Bailey R. Escors D. Minshull J. Santilli G. Thrasher A.J. Collins M.K. Takeuchi Y. Construction of stable packaging cell lines for clinical lentiviral vector production. Sci. Rep. 2015 5 1 9021 10.1038/srep09021 25762005
    [Google Scholar]
  97. Schambach A. Zychlinski D. Ehrnstroem B. Baum C. Biosafety features of lentiviral vectors. Hum. Gene Ther. 2013 24 2 132 142 10.1089/hum.2012.229 23311447
    [Google Scholar]
  98. Ranzani M. Annunziato S. Adams D.J. Montini E. Cancer gene discovery: exploiting insertional mutagenesis. Mol. Cancer Res. 2013 11 10 1141 1158 10.1158/1541‑7786.MCR‑13‑0244 23928056
    [Google Scholar]
  99. Sinn P.L. Sauter S.L. McCray P.B. Jr Gene Therapy Progress and Prospects: Development of improved lentiviral and retroviral vectors – design, biosafety, and production. Gene Ther. 2005 12 14 1089 1098 10.1038/sj.gt.3302570 16003340
    [Google Scholar]
  100. Apolonia L. The old and the new: prospects for non-integrating lentiviral vector technology. Viruses 2020 12 10 1103 10.3390/v12101103 33003492
    [Google Scholar]
  101. Lai C.M. Lai Y.K.Y. Rakoczy P.E. Adenovirus and adeno-associated virus vectors. DNA Cell Biol. 2002 21 12 895 913 10.1089/104454902762053855 12573049
    [Google Scholar]
  102. Link C.J. Adenoviral vectors go retro. Nat. Biotechnol. 2000 18 2 150 151 10.1038/72594 10657118
    [Google Scholar]
  103. Krasnykh V.N. Douglas J.T. van Beusechem V.W. Genetic targeting of adenoviral vectors. Mol. Ther. 2000 1 5 391 405 10.1006/mthe.2000.0062 10933960
    [Google Scholar]
  104. Ahi Y.S. Bangari D.S. Mittal S.K. Adenoviral vector immunity: its implications and circumvention strategies. Curr. Gene Ther. 2011 11 4 307 320 10.2174/156652311796150372 21453277
    [Google Scholar]
  105. Nayak S. Herzog R.W. Progress and prospects: immune responses to viral vectors. Gene Ther. 2010 17 3 295 304 10.1038/gt.2009.148 19907498
    [Google Scholar]
  106. Cots D. Bosch A. Chillón M. Helper dependent adenovirus vectors: progress and future prospects. Curr. Gene Ther. 2013 13 5 370 381 10.2174/156652321305131212125338 24369061
    [Google Scholar]
  107. Bangari D. Mittal S. Current strategies and future directions for eluding adenoviral vector immunity. Curr. Gene Ther. 2006 6 2 215 226 10.2174/156652306776359478 16611043
    [Google Scholar]
  108. Lim F. HSV-1 as a model for emerging gene delivery vehicles. Int. Scholarly Res. Not. 2013 2013 397243 10.5402/2013/397243
    [Google Scholar]
  109. Rao V.B. Feiss M. Mechanisms of DNA packaging by large double-stranded DNA viruses. Annu. Rev. Virol. 2015 2 1 351 378 10.1146/annurev‑virology‑100114‑055212 26958920
    [Google Scholar]
  110. Paterson T. Everett R.D. Mutational dissection of the HSV-1 immediate-early protein Vmw175 involved in transcriptional transactivation and repression. Virology 1988 166 1 186 196 10.1016/0042‑6822(88)90160‑2 2842944
    [Google Scholar]
  111. Burton E.A. Fink D.J. Glorioso J.C. Gene delivery using herpes simplex virus vectors. DNA Cell Biol. 2002 21 12 915 936 10.1089/104454902762053864 12573050
    [Google Scholar]
  112. Kim S.S. Ye C. Kumar P. Chiu I. Subramanya S. Wu H. Shankar P. Manjunath N. Targeted delivery of siRNA to macrophages for anti-inflammatory treatment. Mol. Ther. 2010 18 5 993 1001 10.1038/mt.2010.27 20216529
    [Google Scholar]
  113. Manservigi R. Argnani R. Marconi P. HSV recombinant vectors for gene therapy. Open Virol. J. 2010 4 123 156 20835362
    [Google Scholar]
  114. de Silva S. Bowers W.J. Targeting the central nervous system with herpes simplex virus / Sleeping Beauty hybrid amplicon vectors. Curr. Gene Ther. 2011 11 5 332 340 10.2174/156652311797415845 21711226
    [Google Scholar]
  115. Olschowka J.A. Bowers W.J. Hurley S.D. Mastrangelo M.A. Federoff H.J. Helper-free HSV-1 amplicons elicit a markedly less robust innate immune response in the CNS. Mol. Ther. 2003 7 2 218 227 10.1016/S1525‑0016(02)00036‑9 12597910
    [Google Scholar]
  116. Papadakis E. Nicklin S. Baker A. White S. Promoters and control elements: designing expression cassettes for gene therapy. Curr. Gene Ther. 2004 4 1 89 113 10.2174/1566523044578077 15032617
    [Google Scholar]
  117. Anson D.S. The use of retroviral vectors for gene therapy-what are the risks? A review of retroviral pathogenesis and its relevance to retroviral vector-mediated gene delivery. Genet. Vaccines Ther. 2004 2 1 9 10.1186/1479‑0556‑2‑9 15310406
    [Google Scholar]
  118. Miller D.G. Adam M.A. Miller A.D. Gene transfer by retrovirus vectors occurs only in cells that are actively replicating at the time of infection. Mol. Cell. Biol. 1990 10 8 4239 4242 2370865
    [Google Scholar]
  119. Davidson B.L. Breakefield X.O. Viral vectors for gene delivery to the nervous system. Nat. Rev. Neurosci. 2003 4 5 353 364 10.1038/nrn1104 12728263
    [Google Scholar]
  120. Cesana D. Volpin M. Secanechia Y.N. Montini E. Safety and efficacy of retroviral and lentiviral vectors for gene therapy. Springer 2017 10.1007/978‑3‑319‑53457‑2_2
    [Google Scholar]
  121. Mansouri M. Berger P. Baculovirus for gene delivery to mammalian cells: Past, present and future. Plasmid 2018 98 1 7 10.1016/j.plasmid.2018.05.002 29842913
    [Google Scholar]
  122. Joshi P.R.H. Venereo-Sanchez A. Chahal P.S. Kamen A.A. Advancements in molecular design and bioprocessing of recombinant adeno‐associated virus gene delivery vectors using the insect‐cell baculovirus expression platform. Biotechnol. J. 2021 16 4 2000021 10.1002/biot.202000021 33277815
    [Google Scholar]
  123. Chen C.Y. Lin C.Y. Chen G.Y. Hu Y.C. Baculovirus as a gene delivery vector: Recent understandings of molecular alterations in transduced cells and latest applications. Biotechnol. Adv. 2011 29 6 618 631 10.1016/j.biotechadv.2011.04.004 21550393
    [Google Scholar]
  124. Hu Y.C. Baculoviral vectors for gene delivery: a review. Curr. Gene Ther. 2008 8 1 54 65 10.2174/156652308783688509 18336250
    [Google Scholar]
  125. Hu Y.C. Baculovirus vectors for gene therapy. Adv. Virus Res. 2006 68 287 320 10.1016/S0065‑3527(06)68008‑1 16997015
    [Google Scholar]
  126. Possee R.D. Chambers A.C. Graves L.P. Aksular M. King L.A. Recent developments in the use of baculovirus expression vectors. Curr. Issues Mol. Biol. 2020 34 1 215 230 10.21775/cimb.034.215 31167962
    [Google Scholar]
  127. Palombo F. Monciotti A. Recchia A. Cortese R. Ciliberto G. La Monica N. Site-specific integration in mammalian cells mediated by a new hybrid baculovirus-adeno-associated virus vector. J. Virol. 1998 72 6 5025 5034 10.1128/JVI.72.6.5025‑5034.1998 9573272
    [Google Scholar]
  128. Faísca P. Desmecht D. Sendai virus, the mouse parainfluenza type 1: A longstanding pathogen that remains up-to-date. Res. Vet. Sci. 2007 82 1 115 125 10.1016/j.rvsc.2006.03.009 16759680
    [Google Scholar]
  129. Haridhasapavalan K.K. Borgohain M.P. Dey C. Saha B. Narayan G. Kumar S. Thummer R.P. An insight into non-integrative gene delivery approaches to generate transgene-free induced pluripotent stem cells. Gene 2019 686 146 159 10.1016/j.gene.2018.11.069 30472380
    [Google Scholar]
  130. Ban H. Inoue M. Griesenbach U. Munkonge F. Chan M. Iida A. Alton E.W F W. Hasegawa M. Expression and maturation of Sendai virus vector-derived CFTR protein: functional and biochemical evidence using a GFP-CFTR fusion protein. Gene Ther. 2007 14 24 1688 1694 10.1038/sj.gt.3303032 17898794
    [Google Scholar]
  131. Ura T. Okuda K. Shimada M. Developments in viral vector-based vaccines. Vaccines (Basel) 2014 2 3 624 641 10.3390/vaccines2030624 26344749
    [Google Scholar]
  132. Lee G.K. Maheshri N. Kaspar B. Schaffer D.V. PEG conjugation moderately protects adeno-associated viral vectors against antibody neutralization. Biotechnol. Bioeng. 2005 92 1 24 34 10.1002/bit.20562 15937953
    [Google Scholar]
  133. Le H.T. Yu Q.C. Wilson J.M. Croyle M.A. Utility of PEGylated recombinant adeno-associated viruses for gene transfer. J. Control. Release 2005 108 1 161 177 10.1016/j.jconrel.2005.07.019 16125817
    [Google Scholar]
  134. Miyoshi H. Blömer U. Takahashi M. Gage F.H. Verma I.M. Development of a self-inactivating lentivirus vector. J. Virol. 1998 72 10 8150 8157 10.1128/JVI.72.10.8150‑8157.1998 9733856
    [Google Scholar]
  135. Yip B. Recent advances in CRISPR/Cas9 delivery strategies. Biomolecules 2020 10 6 839 10.3390/biom10060839 32486234
    [Google Scholar]
  136. Liu J. Seol D.W. Helper virus-free gutless adenovirus (HF-GLAd): a new platform for gene therapy. BMB Rep. 2020 53 11 565 575 10.5483/BMBRep.2020.53.11.185 32958121
    [Google Scholar]
  137. Frenkel N. The history of the HSV amplicon: from naturally occurring defective genomes to engineered amplicon vectors. Curr. Gene Ther. 2006 6 3 277 299 10.2174/156652306777591992 16787181
    [Google Scholar]
  138. Hermens W.T.J.M.C. Verhaagen J. Viral vectors, tools for gene transfer in the nervous system. Prog. Neurobiol. 1998 55 4 399 432 10.1016/S0301‑0082(98)00007‑0 9654386
    [Google Scholar]
  139. Whitlow J. Pacelli S. Paul A. Polymeric nanohybrids as a new class of therapeutic biotransporters. Macromol. Chem. Phys. 2016 217 11 1245 1259 10.1002/macp.201500464 29151704
    [Google Scholar]
  140. Yoshizaki M. Hironaka T. Iwasaki H. Ban H. Tokusumi Y. Iida A. Naked Sendai virus vector lacking all of the envelope-related genes: reduced cytopathogenicity and immunogenicity. J. Gene Med. 2006 8 9 1151 1159 10.1002/jgm.938
    [Google Scholar]
  141. Chen Q. Huo K.G. Ji S.M. Pang S.D. Sun T.Y. Niu Y. Jiang Z-H. Zhang P. Han S-X. Li J-Y. Unleashing the potential of mRNA : Overcoming delivery challenges with nanoparticles. Bioeng. Transl. Med. 2024 ••• e10713 10.1002/btm2.10713
    [Google Scholar]
  142. Gill D.R. Pringle I.A. Hyde S.C. Progress and Prospects: The design and production of plasmid vectors. Gene Ther. 2009 16 2 165 171 10.1038/gt.2008.183 19129858
    [Google Scholar]
  143. Kügler S. Kilic E. Bähr M. Human synapsin 1 gene promoter confers highly neuron-specific long-term transgene expression from an adenoviral vector in the adult rat brain depending on the transduced area. Gene Ther. 2003 10 4 337 347 10.1038/sj.gt.3301905 12595892
    [Google Scholar]
  144. Liu Y.P. Berkhout B. miRNA cassettes in viral vectors: problems and solutions. Biochimica et Biophysica Acta (BBA)-. Gene Regulatory Mechanisms. 2011 1809 11-12 732 745
    [Google Scholar]
  145. Leng Q. Chen L. Lv Y. RNA-based scaffolds for bone regeneration: application and mechanisms of mRNA, miRNA and siRNA. Theranostics 2020 10 7 3190 3205 10.7150/thno.42640 32194862
    [Google Scholar]
  146. Watts A. Sankaranarayanan S. Watts A. Raipuria R.K. Optimizing protein expression in heterologous system: Strategies and tools. Meta Gene 2021 29 100899 10.1016/j.mgene.2021.100899
    [Google Scholar]
  147. Gustafsson C. Govindarajan S. Minshull J. Codon bias and heterologous protein expression. Trends Biotechnol. 2004 22 7 346 353 10.1016/j.tibtech.2004.04.006 15245907
    [Google Scholar]
  148. Berry G.E. Asokan A. Cellular transduction mechanisms of adeno-associated viral vectors. Curr. Opin. Virol. 2016 21 54 60 10.1016/j.coviro.2016.08.001 27544821
    [Google Scholar]
  149. Liu D. Zhu M. Zhang Y. Diao Y. Crossing the blood-brain barrier with AAV vectors. Metab. Brain Dis. 2021 36 1 45 52 10.1007/s11011‑020‑00630‑2 33201426
    [Google Scholar]
  150. Tashima T. Smart strategies for therapeutic agent delivery into brain across the blood–brain barrier using receptor-mediated transcytosis. Chem. Pharm. Bull. (Tokyo) 2020 68 4 316 325 10.1248/cpb.c19‑00854 32238649
    [Google Scholar]
  151. Haqqani A.S. Bélanger K. Stanimirovic D.B. Receptor-mediated transcytosis for brain delivery of therapeutics: receptor classes and criteria. Frontiers in Drug Delivery 2024 4 1360302 10.3389/fddev.2024.1360302
    [Google Scholar]
  152. Huang Q. Chan K.Y. Wu J. Botticello-Romero N.R. Zheng Q. Lou S. Keyes C. Svanbergsson A. Johnston J. Mills A. Lin C.Y. Brauer P.P. Clouse G. Pacouret S. Harvey J.W. Beddow T. Hurley J.K. Tobey I.G. Powell M. Chen A.T. Barry A.J. Eid F.E. Chan Y.A. Deverman B.E. An AAV capsid reprogrammed to bind human transferrin receptor mediates brain-wide gene delivery. Science 2024 384 6701 1220 1227 10.1126/science.adm8386 38753766
    [Google Scholar]
  153. Gkouvatsos K. Papanikolaou G. Pantopoulos K. Regulation of iron transport and the role of transferrin. Biochim. Biophys. Acta, Gen. Subj. 2012 1820 3 188 202 10.1016/j.bbagen.2011.10.013
    [Google Scholar]
  154. Banks W.A. Owen J.B. Erickson M.A. Insulin in the brain: There and back again. Pharmacol. Ther. 2012 136 1 82 93 10.1016/j.pharmthera.2012.07.006 22820012
    [Google Scholar]
  155. Johnson J.S. Samulski R.J. Enhancement of adeno-associated virus infection by mobilizing capsids into and out of the nucleolus. J. Virol. 2009 83 6 2632 2644 10.1128/JVI.02309‑08 19109385
    [Google Scholar]
  156. Suk J.S. Xu Q. Kim N. Hanes J. Ensign L.M. PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Adv. Drug Deliv. Rev. 2016 99 Pt A 28 51 10.1016/j.addr.2015.09.012 26456916
    [Google Scholar]
  157. Yan Y. Liu X.Y. Lu A. Wang X.Y. Jiang L.X. Wang J.C. Non-viral vectors for RNA delivery. J. Control. Release 2022 342 241 279 10.1016/j.jconrel.2022.01.008 35016918
    [Google Scholar]
  158. Tasset A. Bellamkonda A. Wang W. Pyatnitskiy I. Ward D. Peppas N. Wang H. Overcoming barriers in non-viral gene delivery for neurological applications. Nanoscale 2022 14 10 3698 3719 10.1039/D1NR06939J 35195645
    [Google Scholar]
  159. Duan X. Li Y. Physicochemical characteristics of nanoparticles affect circulation, biodistribution, cellular internalization, and trafficking. Small 2013 9 9-10 1521 1532 10.1002/smll.201201390 23019091
    [Google Scholar]
  160. Gajbhiye K.R. Pawar A. Mahadik K.R. Gajbhiye V. PEGylated nanocarriers: A promising tool for targeted delivery to the brain. Colloids Surf. B Biointerfaces 2020 187 110770 10.1016/j.colsurfb.2019.110770 31926790
    [Google Scholar]
  161. Wang Y. Bruggeman K.F. Franks S. Gautam V. Hodgetts S.I. Harvey A.R. Williams R.J. Nisbet D.R. Is viral vector gene delivery more effective using biomaterials? Adv. Healthc. Mater. 2021 10 1 2001238 10.1002/adhm.202001238 33191667
    [Google Scholar]
  162. Bao Y. Jin Y. Chivukula P. Zhang J. Liu Y. Liu J. Clamme J.P. Mahato R.I. Ng D. Ying W. Wang Y. Yu L. Effect of PEGylation on biodistribution and gene silencing of siRNA/lipid nanoparticle complexes. Pharm. Res. 2013 30 2 342 351 10.1007/s11095‑012‑0874‑6 22983644
    [Google Scholar]
  163. Patel M.M. Goyal B.R. Bhadada S.V. Bhatt J.S. Amin A.F. Getting into the Brain. CNS Drugs 2009 23 1 35 58 10.2165/0023210‑200923010‑00003 19062774
    [Google Scholar]
  164. Helms H.C.C. Kristensen M. Saaby L. Fricker G. Brodin B. Drug delivery strategies to overcome the blood–brain barrier (BBB). Physiology, Pharmacology and Pathology of the Blood-Brain Barrier. Springer 2020 151 183
    [Google Scholar]
  165. Timbie K.F. Mead B.P. Price R.J. Drug and gene delivery across the blood–brain barrier with focused ultrasound. J. Control. Release 2015 219 61 75 10.1016/j.jconrel.2015.08.059 26362698
    [Google Scholar]
  166. Chen K.T. Wei K.C. Liu H.L. Theranostic strategy of focused ultrasound induced blood-brain barrier opening for CNS disease treatment. Front. Pharmacol. 2019 10 86 10.3389/fphar.2019.00086 30792657
    [Google Scholar]
  167. Meairs S. Facilitation of drug transport across the blood–brain barrier with ultrasound and microbubbles. Pharmaceutics 2015 7 3 275 293 10.3390/pharmaceutics7030275 26404357
    [Google Scholar]
  168. Fan C.H. Ting C.Y. Lin H.J. Wang C.H. Liu H.L. Yen T.C. Yeh C.K. SPIO-conjugated, doxorubicin-loaded microbubbles for concurrent MRI and focused-ultrasound enhanced brain-tumor drug delivery. Biomaterials 2013 34 14 3706 3715 10.1016/j.biomaterials.2013.01.099 23433776
    [Google Scholar]
  169. Ji R. Karakatsani M.E. Burgess M. Smith M. Murillo M.F. Konofagou E.E. Cavitation-modulated inflammatory response following focused ultrasound blood-brain barrier opening. J. Control. Release 2021 337 458 471 10.1016/j.jconrel.2021.07.042 34324895
    [Google Scholar]
  170. Ruan S. Zhou Y. Jiang X. Gao H. Rethinking CRITID procedure of brain targeting drug delivery: circulation, blood brain barrier recognition, intracellular transport, diseased cell targeting, internalization, and drug release. Adv. Sci. (Weinh.) 2021 8 9 2004025 10.1002/advs.202004025 33977060
    [Google Scholar]
  171. Guo Y. Lee H. Fang Z. Velalopoulou A. Kim J. Thomas M.B. Liu J. Abramowitz R.G. Kim Y. Coskun A.F. Krummel D.P. Sengupta S. MacDonald T.J. Arvanitis C. Single-cell analysis reveals effective siRNA delivery in brain tumors with microbubble-enhanced ultrasound and cationic nanoparticles. Sci. Adv. 2021 7 18 eabf7390 10.1126/sciadv.abf7390 33931452
    [Google Scholar]
  172. Kügler S. Meyn L. Holzmüller H. Gerhardt E. Isenmann S. Schulz J.B. Bähr M. Neuron-specific expression of therapeutic proteins: evaluation of different cellular promoters in recombinant adenoviral vectors. Mol. Cell. Neurosci. 2001 17 1 78 96 10.1006/mcne.2000.0929 11161471
    [Google Scholar]
  173. Wayman G.A. Tokumitsu H. Davare M.A. Soderling T.R. Analysis of CaM-kinase signaling in cells. Cell Calcium 2011 50 1 1 8 10.1016/j.ceca.2011.02.007 21529938
    [Google Scholar]
  174. Snow W.M. Albensi B.C. Neuronal gene targets of NF-κB and their dysregulation in Alzheimer’s disease. Front. Mol. Neurosci. 2016 9 118 10.3389/fnmol.2016.00118 27881951
    [Google Scholar]
  175. Aurélie D. Carole E. Nicole D. Lentiviral vectors: a powerful tool to target astrocytes in vivo. Curr. Drug Targets 2013 14 11 1336 1346 10.2174/13894501113146660213 24020977
    [Google Scholar]
  176. Brenner M. Messing A. Regulation of GFAP Expression. ASN Neuro 2021 13 10.1177/1759091420981206 33601918
    [Google Scholar]
  177. Grimm D. Small silencing RNAs: State-of-the-art. Adv. Drug Deliv. Rev. 2009 61 9 672 703 10.1016/j.addr.2009.05.002 19427885
    [Google Scholar]
  178. Lentz T.B. Gray S.J. Samulski R.J. Viral vectors for gene delivery to the central nervous system. Neurobiol. Dis. 2012 48 2 179 188 10.1016/j.nbd.2011.09.014 22001604
    [Google Scholar]
  179. Wang D. Tai P.W.L. Gao G. Adeno-associated virus vector as a platform for gene therapy delivery. Nat. Rev. Drug Discov. 2019 18 5 358 378 10.1038/s41573‑019‑0012‑9 30710128
    [Google Scholar]
  180. Terstappen G.C. Meyer A.H. Bell R.D. Zhang W. Strategies for delivering therapeutics across the blood–brain barrier. Nat. Rev. Drug Discov. 2021 20 5 362 383 10.1038/s41573‑021‑00139‑y 33649582
    [Google Scholar]
  181. Huang Q. Chen A.T. Chan K.Y. Sorensen H. Barry A.J. Azari B. Zheng Q. Beddow T. Zhao B. Tobey I.G. Moncada-Reid C. Eid F.E. Walkey C.J. Ljungberg M.C. Lagor W.R. Heaney J.D. Chan Y.A. Deverman B.E. Targeting AAV vectors to the central nervous system by engineering capsid–receptor interactions that enable crossing of the blood–brain barrier. PLoS Biol. 2023 21 7 e3002112 10.1371/journal.pbio.3002112 37467291
    [Google Scholar]
  182. Goertsen D. Flytzanis N.C. Goeden N. Chuapoco M.R. Cummins A. Chen Y. Fan Y. Zhang Q. Sharma J. Duan Y. Wang L. Feng G. Chen Y. Ip N.Y. Pickel J. Gradinaru V. AAV capsid variants with brain-wide transgene expression and decreased liver targeting after intravenous delivery in mouse and marmoset. Nat. Neurosci. 2022 25 1 106 115 10.1038/s41593‑021‑00969‑4 34887588
    [Google Scholar]
  183. Nectow A.R. Nestler E.J. Viral tools for neuroscience. Nat. Rev. Neurosci. 2020 21 12 669 681 10.1038/s41583‑020‑00382‑z 33110222
    [Google Scholar]
  184. Zheng Q.C. Jiang S. Wu Y.Z. Shang D. Zhang Y. Hu S.B. Cheng X. Zhang C. Sun P. Gao Y. Song Z.F. Li M. Dual-targeting nanoparticle-mediated gene therapy strategy for hepatocellular carcinoma by delivering small interfering RNA. Front. Bioeng. Biotechnol. 2020 8 512 10.3389/fbioe.2020.00512 32587849
    [Google Scholar]
  185. Taghipour Y.D. Zarebkohan A. Salehi R. Rahimi F. Torchilin V.P. Hamblin M.R. Seifalian A. An update on dual targeting strategy for cancer treatment. J. Control. Release 2022 349 67 96 10.1016/j.jconrel.2022.06.044 35779656
    [Google Scholar]
  186. Joshi C.R. Labhasetwar V. Ghorpade A. Destination brain: the past, present, and future of therapeutic gene delivery. J. Neuroimmune Pharmacol. 2017 12 1 51 83 10.1007/s11481‑016‑9724‑3 28160121
    [Google Scholar]
  187. Ch’ng A.C.W. Lam P. Alassiri M. Lim T.S. Application of phage display for T-cell receptor discovery. Biotechnol. Adv. 2022 54 107870 10.1016/j.biotechadv.2021.107870 34801662
    [Google Scholar]
  188. Gera N. Hussain M. Rao B.M. Protein selection using yeast surface display. Methods 2013 60 1 15 26 10.1016/j.ymeth.2012.03.014 22465794
    [Google Scholar]
  189. Singh P. Gonzalez M.J. Manchester M. Viruses and their uses in nanotechnology. Drug Dev. Res. 2006 67 1 23 41 10.1002/ddr.20064
    [Google Scholar]
  190. Zheng M. Tao W. Zou Y. Farokhzad O.C. Shi B. Nanotechnology-based strategies for siRNA brain delivery for disease therapy. Trends Biotechnol. 2018 36 5 562 575 10.1016/j.tibtech.2018.01.006 29422412
    [Google Scholar]
  191. Tai W. Gao X. Functional peptides for siRNA delivery. Adv. Drug Deliv. Rev. 2017 110-111 157 168 10.1016/j.addr.2016.08.004 27530388
    [Google Scholar]
  192. Wiseman A.C. Immunosuppressive Medications. Clin. J. Am. Soc. Nephrol. 2016 11 2 332 343 10.2215/CJN.08570814 26170177
    [Google Scholar]
  193. Gower R.M. Boehler R.M. Azarin S.M. Ricci C.F. Leonard J.N. Shea L.D. Modulation of leukocyte infiltration and phenotype in microporous tissue engineering scaffolds via vector induced IL-10 expression. Biomaterials 2014 35 6 2024 2031 10.1016/j.biomaterials.2013.11.036 24309498
    [Google Scholar]
  194. Sushnitha M. Evangelopoulos M. Tasciotti E. Taraballi F. Cell membrane-based biomimetic nanoparticles and the immune system: immunomodulatory interactions to therapeutic applications. Front. Bioeng. Biotechnol. 2020 8 627 10.3389/fbioe.2020.00627 32626700
    [Google Scholar]
  195. Elmer B.M. Swanson K.A. Bangari D.S. Piepenhagen P.A. Roberts E. Taksir T. Guo L. Obinu M.C. Barneoud P. Ryan S. Zhang B. Pradier L. Yang Z.Y. Nabel G.J. Gene delivery of a modified antibody to Aβ reduces progression of murine Alzheimer’s disease. PLoS One 2019 14 12 e0226245 10.1371/journal.pone.0226245 31887144
    [Google Scholar]
  196. Zhao L. Gottesdiener A.J. Parmar M. Li M. Kaminsky S.M. Chiuchiolo M.J. Sondhi D. Sullivan P.M. Holtzman D.M. Crystal R.G. Paul S.M. Intracerebral adeno-associated virus gene delivery of apolipoprotein E2 markedly reduces brain amyloid pathology in Alzheimer’s disease mouse models. Neurobiol. Aging 2016 44 159 172 10.1016/j.neurobiolaging.2016.04.020 27318144
    [Google Scholar]
  197. Sánchez-Sarasúa S. Ribes-Navarro A. Beltrán-Bretones M.T. Sánchez-Pérez A.M. AAV delivery of shRNA against IRS1 in GABAergic neurons in rat hippocampus impairs spatial memory in females and male rats. Brain Struct. Funct. 2021 226 1 163 178 10.1007/s00429‑020‑02155‑x 33245394
    [Google Scholar]
  198. Ghauri M.S. Ou L. AAV engineering for improving tropism to the central nervous system. Biology (Basel) 2023 12 2 186 10.3390/biology12020186 36829465
    [Google Scholar]
  199. Wagner E. Polymers for siRNA delivery: inspired by viruses to be targeted, dynamic, and precise. Acc. Chem. Res. 2012 45 7 1005 1013 10.1021/ar2002232 22191535
    [Google Scholar]
  200. Nigatu A.S. Vupputuri S. Flynn N. Ramsey J.D. Effects of cell-penetrating peptides on transduction efficiency of PEGylated adenovirus. Biomed. Pharmacother. 2015 71 153 160 10.1016/j.biopha.2015.02.015 25960231
    [Google Scholar]
  201. Kavanagh E.W. Green J.J. Toward gene transfer nanoparticles as therapeutics. Adv. Healthc. Mater. 2022 11 7 2102145 10.1002/adhm.202102145 35006646
    [Google Scholar]
  202. Markesbery W.R. Neuropathologic alterations in mild cognitive impairment: a review. J. Alzheimers Dis. 2010 19 1 221 228 10.3233/JAD‑2010‑1220 20061641
    [Google Scholar]
  203. Coughlin D. Irwin D.J. Emerging diagnostic and therapeutic strategies for tauopathies. Curr. Neurol. Neurosci. Rep. 2017 17 9 72 10.1007/s11910‑017‑0779‑1 28785992
    [Google Scholar]
  204. Mangalmurti A. Lukens J.R. How neurons die in Alzheimer’s disease: Implications for neuroinflammation. Curr. Opin. Neurobiol. 2022 75 102575 10.1016/j.conb.2022.102575 35691251
    [Google Scholar]
  205. Onyango I.G. Jauregui G.V. Čarná M. Bennett J.P. Jr Stokin G.B. Neuroinflammation in Alzheimer’s disease. Biomedicines 2021 9 5 524 10.3390/biomedicines9050524 34067173
    [Google Scholar]
  206. Zuckerman J.E. Davis M.E. Clinical experiences with systemically administered siRNA-based therapeutics in cancer. Nat. Rev. Drug Discov. 2015 14 12 843 856 10.1038/nrd4685 26567702
    [Google Scholar]
  207. Ferguson C.M. Hildebrand S. Godinho B.M.D.C. Buchwald J. Echeverria D. Coles A. Grigorenko A. Vangjeli L. Sousa J. McHugh N. Hassler M. Santarelli F. Heneka M.T. Rogaev E. Khvorova A. Silencing Apoe with divalent‐siRNAs improves amyloid burden and activates immune response pathways in Alzheimer’s disease. Alzheimers Dement. 2024 20 4 2632 2652 10.1002/alz.13703 38375983
    [Google Scholar]
  208. Kolli N. Lu M. Maiti P. Rossignol J. Dunbar G.L. Application of the gene editing tool, CRISPR-Cas9, for treating neurodegenerative diseases. Neurochem. Int. 2018 112 187 196 10.1016/j.neuint.2017.07.007 28732771
    [Google Scholar]
  209. Patel M.M. Patel B.M. Crossing the blood–brain barrier: recent advances in drug delivery to the brain. CNS Drugs 2017 31 2 109 133 10.1007/s40263‑016‑0405‑9 28101766
    [Google Scholar]
  210. Rawal S.U. Patel B.M. Patel M.M. New drug delivery systems developed for brain targeting. Drugs 2022 82 7 749 792 10.1007/s40265‑022‑01717‑z 35596879
    [Google Scholar]
  211. Chakradhar S. Predictable response: Finding optimal drugs and doses using artificial intelligence. Nat. Med. 2017 23 11 1244 1247 10.1038/nm1117‑1244 29117178
    [Google Scholar]
  212. Martinelli D.D. Machine learning for siRNA efficiency prediction: A systematic review. Heal. Sci. Rev. 2024 11 100157 10.1016/j.hsr.2024.100157
    [Google Scholar]
  213. Rafii M.S. Tuszynski M.H. Thomas R.G. Barba D. Brewer J.B. Rissman R.A. Siffert J. Aisen P.S. Adeno-associated viral vector (serotype 2)–nerve growth factor for patients with alzheimer disease: a randomized clinical trial. JAMA Neurol. 2018 75 7 834 841 10.1001/jamaneurol.2018.0233 29582053
    [Google Scholar]
  214. Tuszynski M.H. Yang J.H. Barba D. U H.S. Bakay R.A.E. Pay M.M. Masliah E. Conner J.M. Kobalka P. Roy S. Nagahara A.H. Nerve growth factor gene therapy: activation of neuronal responses in Alzheimer disease. JAMA Neurol. 2015 72 10 1139 1147 10.1001/jamaneurol.2015.1807 26302439
    [Google Scholar]
  215. Zhao Z. Anselmo A.C. Mitragotri S. Viral vector‐based gene therapies in the clinic. Bioeng. Transl. Med. 2022 7 1 e10258 10.1002/btm2.10258 35079633
    [Google Scholar]
  216. Iwasaki Y. Negishi T. Inoue M. Tashiro T. Tabira T. Kimura N. Sendai virus vector‐mediated brain‐derived neurotrophic factor expression ameliorates memory deficits and synaptic degeneration in a transgenic mouse model of Alzheimer’s disease. J. Neurosci. Res. 2012 90 5 981 989 10.1002/jnr.22830 22252710
    [Google Scholar]
  217. Li Y. Wang J. Zhang S. Liu Z. Neprilysin gene transfer: A promising therapeutic approach for Alzheimer’s disease. J. Neurosci. Res. 2015 93 9 1325 1329 10.1002/jnr.23564 26096375
    [Google Scholar]
/content/journals/cpb/10.2174/0113892010334094241112190337
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Impact and Significance of Viral Vectors for siRNA Delivery in the Treatment of Alzheimer’s Disease
Bentham Science Publishers ; https://doi.org/10.2174/0113892010334094241112190337
/content/journals/cpb/10.2174/0113892010334094241112190337
/content/journals/cpb/10.2174/0113892010334094241112190337
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  • Article Type:     Review Article
Keywords: Alzheimer’s disease ; siRNA ; neurodegeneration ; delivery strategies ; viral vectors ; blood-brain barrier

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