Viral Vectors in Gene Therapy

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Viral vectors are one of the major vechicles used by scientists in gene therapy to get their sequences expressed in the proper host. There are a myrid of possible viral vectors. This is an area of continual new development in gene therapy. These lectures give background to some of the viral vectors. The lectures will be updated as new developments occur.

Retroviral Vectors
(HIV)
(MLV)
Adenoviral Vectors
Other Viral Vectors (HSV, AAV)

Introduction

Learning Objectives

Development of viral vectors. The modification of viruses for the delivery of exogenous genes was first reported in 1968. These early attempts using the tobacco mosaic virus showed that viruses could be used to transfer specific genetic material into cells. Studies rapidly shifted to viruses capable of infecting mammalian cells and led to development of a recombinantly modified simian papilloma virus, SV40. With the advent of the now commonplace recombinant DNA techniques, these vectors were capable of transferring and expressing the rabbit -globulin gene in culture. The first recombinant vectors of relevance to the field of human gene therapy were the retroviruses. The development of helper-free packaging cell lines in 1989 marked the advent of retroviral vectors as efficient gene therapeutic agents.

Retroviral and other viral vectors. While other recombinant viral vector systems have been developed, retroviral vectors remain the most popular vector system for gene therapy protocols. This may in part be due to their historical significance as the first vectors developed for efficient gene therapy and the infancy of the field of gene therapy. Vector systems to be described in this lecture include retroviral, adenoviral, adeno-associated, herpes simplex, and vaccinia vectors. Discussion will focus on the basic biology of these viruses and vector preparation, as well as their applications and limitations in gene therapeutics.

Viral Vector Comparison

VectorInsert SizeIntegrateTiterTransduction efficiencyMajor advantage(s)Major obstacle(s)
MMLV <8kBYes106 HighStable transfection of dividing cellsInfects only rapidly dividing cells
Adeno<7.5kBNo1012High Transfects nearly all cell types dividing or nondividingTransient expression triggers immune response, common human virus
AAV<4kBYes (?)106High Stable transfectionSmall insert size, integration poorly understood
HSV<20kBNo 1010LowLarge insert size. Neuron specificityTransient expression, potential to generate infectious HSV in humans
Vaccinia <25kBNoN/A HighInfects a variety of cells effectively.Limited to non- small pox vaccinated or immuncompromised individuals

last updated 7/29/96