Current Gene Therapy - Volume 3, Issue 6, 2003

Biosafety of viral vectors was first conceived as a set of guidelines for the risk assessment and management of viral vectors under various research and development situations. People from academia or industrial area concerned with basic research, gene therapy and vaccine technologies, were demanding ways to improve their daily research practices or production activities, their in vivo experiments and their clinical trials with Read More

For people starting off in the field of gene therapy, the encountered terminology is often quite confusing. Moreover, the background on basic virology may be modest. The following introduction provides a head start to any novice willing to gain more in-depth knowledge on the subject. The development of gene therapy is also addressed from a historical perspective.

Extensive gene therapy studies in preclinical models and in clinical trials underscore the relative safety of onco-retroviral vectors. Up until recently, no adverse effects have been reported in nearly 2000 patients that were enrolled in gene therapy clinical trials involving oncoretroviral vectors. However, the main safety concern of using onco-retroviral vectors is related to the risk of malignant transformation following oncogene Read More

The characteristics of lentiviral vectors (stable integration in non-dividing and dividing cells, long-term expression of the transgene, absence of immune response) make them ideal gene transfer vehicula for future gene therapy. However, the most potent lentiviral vectors are derived from highly pathogenic human viruses, such as HIV. We describe how the field has engineered lentivectors with increasing biosafety both for t Read More

Adenoviral vectors can efficiently transduce a broad variety of different cell types and have been used extensively in preclinical and clinical studies. However, early generation of adenoviral vectors retained residual adenoviral genes that contribute to inflammatory immune responses and toxicity. In addition, these vectors often result in transient expression of the potentially therapeutic transgene. Some clinical trials based on early Read More

Recombinant AAV efficacy has been demonstrated in numerous gene therapy preclinical studies. As this vector is increasingly applied to human clinical trials, it is a priority to evaluate the risks of its use for workers involved in research and clinical trials as well as for the patients and their descendants. At high multiplicity of infection, wild-type AAV integrates into human chromosome 19 in ∼60% of latently infected cell lines Read More

Autonomous parvoviruses are small, non-enveloped, lytic DNA viruses replicating in the nucleus of actively dividing mammalian cells of appropriate species and tissue origins. In contrast to AAV, the other main subgroup of parvoviruses, autonomous parvoviruses do not require the assistance of an auxiliary virus for productive infection and do not stably integrate in the cellular DNA. Therefore, autonomous parvoviruses are suitab Read More

Poxviruses have played an amazing role in the development of virology, immunology and vaccinology. In 1796, deliberate inoculation of cowpox virus to humans was proved by Dr. Edward Jenner to protect against the antigenically related smallpox virus (variola). This discovery founded the science of immunology and eventually led to smallpox eradication from the earth in 1980 after a world wide vaccination campaign with Read More

Herpesviruses are large DNA viruses, which possess a number of advantages as gene delivery vectors. These relate to an ability to package large DNA insertions and establish lifelong latent infections in which the viral genome exists as a stable episome in the nucleus. For gene therapy to become a potential future treatment option, biosafe therapeutically efficient gene transfer is a central, but more and more stringent req Read More