Current Gene Therapy - Volume 6, Issue 3, 2006

The study by Richard R. Spaete and Niza Frenkel [Spaete et al., 1982] that can be considered as the birth of the concept of herpes simplex virus type 1 (HSV-1) amplicons was published almost 25 years ago, giving us a good opportunity to celebrate this event. That paper was actually the climax of a series of very elegant and clever fundamental studies aimed to identify and characterize the origins of virus DNA replication, Read More

The HSV amplicon vector was derived in 1981/1982 after elaborate experience with "defective viruses", arising spontaneously in viral stocks propagated at high multiplicities of infection (m.o.i.). The defective viruses were found to contain large concatemeric genomes with repeat units of limited complexity. We employed cloned defective genome repeats to generate the "amplicon" vectors, which in the presence of helper Read More

The herpes simplex virus (HSV) amplicon vector is a versatile plasmid-based gene delivery vehicle with a large transgene capacity (up to 150 kb) and the ability to infect a broad range of cell types. The vector system was originally developed by Frenkel and her colleagues in 1980. Ever since, a great deal of effort by various investigators has been directed at minimizing the toxicity associated with the inevitable contamination by Read More

Chimeric or hybrid herpes simplex virus type 1/adeno-associated virus amplicon vectors combine the large transgene capacity of HSV-1 with the potential for site-specific genomic integration and stable transgene expression of AAV. These chimeric vectors have been demonstrated to support transgene expression for significantly longer periods than standard HSV-1 amplicons. Moreover, HSV/AAV hybrid vectors can mediate int Read More

The principal aim of gene therapy for recessive genetic diseases is to supplement the loss of function of an endogenous gene. For the treatment of many diseases regulation of transgene expression at physiological levels, expression of multiple splice variants, and correct tissue specificity are of utmost importance for effective therapy. We therefore believe the use of a complete genomic locus, in which the native promoter and r Read More

Strategies that employ HSV amplicon vectors in the prevention and/or amelioration of pathogenic states afflicting the central nervous system (CNS) have been extensively documented in preclinical disease models. The versatility of the HSV amplicon platform allows for the implementation of therapeutic approaches that require expression of genes exhibiting neuroprotective or neuroplastic activities, or even applications that Read More

This review summarizes recent data on the use of HSV-1-based amplicon vectors for in vivo gene delivery to the brains of rats and mice to study and modify behaviour. Here we describe studies that have focused on cognitive functions like learning and memory. In addition, the use of amplicons in other behavioural studies, like addiction, social interaction, anxiety and stress, will be briefly updated. Several remarkable fi Read More

HSV amplicon vectors provide a unique tool in the armamentarium of weapons for treatment of cancer. Their large capacity (up to 150 kb) allows incorporation of multiple and large transgenes, including whole gene loci, as well as components of other viruses to control the fate of transgenes in the host cells. Means have been developed to achieve heritable transmission of transgenes in tumor cells by episomal replication or g Read More

HSV-1 amplicon vectors have been considered as a promising gene delivery system for gene therapy of skeletal muscle diseases, due to the ability to infect non-dividing cells such as differentiated muscle cells, and to accommodate large transgenes such as the 14-kb dystrophin cDNA. Studies revealed that HSV-1 amplicons can transduce cultured differentiated and undifferentiated muscle cells with high efficiency. Studies also r Read More

HSV-1 amplicon vectors efficiently transduce cultured antigen-presenting cells (APC), including both human and murine dendritic cells as well as primary human chronic lymphocytic leukemia (CLL) B cells. Helper-free amplicons have been shown to be especially well-suited for this purpose, since they do not impair the antigen-presenting functions of these target cells. In vivo, amplicon vectors have been used in preclinical st Read More

The lack of efficient systems for the propagation of the hepatitis C virus in vitro, in the past decade, led to the development of several heterologous expression systems for the study of the HCV proteins and the HCV life cycle. HSV- 1 amplicon vectors encoding the HCV structural and some of the non structural proteins were generated initially for the expression of high levels of these proteins into mammalian cells. The recent deve Read More

Amplicon-6 and Tamplicon-7 are novel non-integrating vectors derived from the lymphotropic Human Herpesviruses 6 and 7 (HHV-6 and HHV-7). In the presence of helper viruses the amplicon vectors replicate to yield packaged defective genomes of size approximately 150 kb and consisting of multiple repeat units containing (i) the oriLyt DNA replication origin (ii) the pac-1 and pac-2 cleavage and packaging signals (iii) bacterial Read More