Viral Vectors for Gene Therapy


Viruses can be engineered to deliver genetic material to cells without causing disease. Viral gene therapy vectors have therapeutic use in the treatment of hereditary disease, infectious diseases and cancer as well as for vaccine development.

Keywords: retrovirus; lentivirus; adenovirus; adeno‐associated virus

Figure 1.

Schematic representations of oncolytic virus function. (a) Retroviral vectors transduce only dividing cells such as cancer cells. The retroviral vector is engineered to express a suicide gene that induces cell death. Since only dividing cells are transduced by the vector, only these are killed by the vector and normal, quiescent cells survive. (b) Replication‐deficient vectors. Viruses such as adenovirus encode genes that mediate cell lysis as a normal part of their viral life cycle. If these genes are removed in the vector, lysis does not occur in normal cells. However cancer cells may downregulate cellular genes that usually block lysis (such as p53), thus permitting viral replication and cancer cell lysis thereby allowing the vector to spread through the tumour, selectively killing cancer cells and leaving normal cells in tact.

Figure 2.

Schematic representation of nonintegrating lentiviral vector transgene expression. Three different forms of episomal vector DNA are present in the transduced cell; one linear and two circular forms, the first containing two long‐terminal repeats (2‐LTR circles) and the second containing 1‐LTR (1‐LTR circles). All episomes are transcribed but the relative efficiency of transcription from each form is not known.

Figure 3.

Schematic overview of the wild type (wt) and recombinant adeno‐associated virus (rAAV) life cycles. In the presence of helper virus both wt and rAAV enter the lytic phase of their life cycle during which viral replication occurs. In the absence of helper virus wtAAV latently infects cells when it is integrated into the AAVS1 site of human chromosome 19. Subsequent infection with helper virus allows replication of the integrated wtAAV genome. During a latent infection of rAAV the genome remains mainly episomal but it can undergo random integration into regions with double‐stranded breaks (Prom., Promoter).



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Further Reading

Bernard NF, David MK, Peter MH et al. (2007) Fields Virology. Lippincott Williams & Wilkins.

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How to Cite close
Philpott, Nicola J(Sep 2007) Viral Vectors for Gene Therapy. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0020707]