Retroviral Vectors

David M Nelson and Richard A Morgan, Gene Transfer Technology Section, Clinical Gene Therapy Branch, Human Genome Research Institute, National Institutes of Health, Maryland, USA

Viral vectors have become one of the most widely used agents for gene transfer studies. These vectors have received so much attention primarily because they are more efficient at mediating gene transfer than other methods such as electroporation, transfec-tion, lipofection, and particle acceleration. They act like Trojan horses to carry and deliver therapeutic transgenes into target cells. Viral vectors have been made based on retrovirus, adenovirus, adeno-associated virus (AAV), Epstein-Barr virus (EBV), herpes simplex virus (HSV), and alphaviruses including Semliki Forest virus and Sindbis virus.

Of these, retroviral vectors have received the greatest attention.

Retroviral vectors are retroviruses which have been genetically engineered to deliver therapeutic genes rather than retroviral genes to target cells. Retroviral vectors are particularly attractive because the transgenes they carry integrate into the target genome and can potentially provide permanent gene expression. Other viral vector systems have disadvantages in that they do not integrate (adenoviruses, EBV), are more pathogenic (adenoviruses. EBV and HSV), require helper viruses which are difficult to eliminate (AAV), may be toxic to target cells (EBV, adenovirus and alphaviruses), or require transient production strategies which are subject to variability (AAV, adenovirus and alphaviruses). For these reasons, retroviruses have been the vector of choice in most of the clinical gene therapy trials to date.

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