Abstract
The majority of viral vectors currently used possess modest cargo capability (up to 40 kb) being based on retroviruses, lentiviruses, adenoviruses, and adenoassociated viruses. These vectors have made the most rapid transition from laboratory to clinic because their small genomes have simplified their characterization and modification. However, there is now an increasing need both in research and therapy to complement this repertoire with larger capacity vectors able to deliver multiple transgenes or to encode complex regulatory regions, constructs which can easily span more than 100 kb. Herpes Simplex Virus Type I (HSV-1) is a well-characterized human virus which is able to package about 150 kb of DNA, and several vector systems are currently in development for gene transfer applications, particularly in neurons where other systems have low efficiency. However, to reach the same level of versatility and ease of use as that of smaller genome viral vectors, simple systems for high-titer production must be developed. This paper reviews the major HSV-1 vector systems and analyses the common elements which may be most important to manipulate to achieve this goal.
Highlights
Horizontal gene transfer has long been recognized as an important factor in microbial evolution it is only recently that it has been recognized as a widespread phenomenon in multicellular eukaryotes [4,5,6]
Recombinant genomic vectors deleted for multiple genes to reduce toxicity or to accommodate larger transgenes become progressively harder to grow as more viral genes are deleted and have to be supplied by a complementing cell line
Amplicon packaging by cotransfection with Herpes Simplex Virus Type 1 (HSV-1) bacterial artificial chromosomes (BACs) plasmids suffers from the limited titer produced by transfected cells, in part due to the severe alteration of cellular metabolism provoked by the transfection procedure
Summary
Horizontal gene transfer has long been recognized as an important factor in microbial evolution (reviewed in [1,2,3]) it is only recently that it has been recognized as a widespread phenomenon in multicellular eukaryotes [4,5,6]. Taking example from the exquisite specificity and efficiency of viruses to change the phenotype of the cells which they infect, attempts to make gene transfer tools have relied heavily on viral vectors (reviewed in [12,13,14,15,16]). This field of “vectorology” has followed a synthetic biology approach, using both natural and engineered components to construct gene delivery vehicles tailored to specific research or therapeutic aims. While much research and development remain to fully master the task of reliable and efficient transgene expression using the compact and streamlined vectors based on small viruses, there is a growing need to explore larger platforms for assembling networks of genes, to better understand and manipulate interactions among their products and regulatory regions
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