Retroviral Vectors in Gene Therapy


Retroviruses have a positive‐strand nonsegmented RNA genome that undergoes reverse transcription to a double‐stranded DNA form prior to random integration into the genome of a target cell in a form called the provirus. The provirus is transcribed into mRNAs that encode the viral proteins, and these proteins package the full‐length genomic mRNA into virions to complete the virus life cycle. Retroviral vectors are retroviruses engineered to transfer and integrate specific DNA sequences into the genomes of target cells, and are often designed to be replication‐defective to avoid further spread after the initial transfer event. Gene transfer and expression by a replication‐defective retroviral vector is referred to as transduction to differentiate this process from infection by a typical virus that leads to virus production and spread.

Keywords: retroviral vector; lentiviral vector; packaging cells; gene therapy

Figure 1.

The structure of a simple replication‐competent retrovirus and derivative components used to produce retroviral vectors. (a) The DNA provirus structure of a simple oncoretrovirus, Moloney murine leukemia virus. RNAs transcribed from the provirus are shown at the bottom. (b) Packaging DNAs encode the viral proteins required for virus replication and are introduced into eukaryotic cells to make retrovirus packaging cells. (c) LXL is a minimal retroviral vector with all elements required for efficient transfer and a cloning site for insertion of genes or other sequence elements. LASN is an example of a retrovirus vector that encodes human adenosine deaminase and bacterial neomycin phosphotransferase. This was the vector used in the first human gene therapy trial to treat severe combined immunodeficiency due to lack of adenosine deaminase (see text). LTR: ; SD: ; SA: ; pA: ; ADA: adenosine deaminase; SV: simian virus‐40 promoter and enhancers; neo: bacterial neomycin phosphotransferase cDNA; Wavy lines: polyA sequences. Diagrams are drawn to scale and the scale marker indicates 1 kb length.



Blaese RM, Culver KW, Miller AD, et al. (1995) T lymphocyte‐directed gene therapy for ADA‐SCID: initial trial results after 4 years. Science 270: 475–480.

Cavazzana‐Calvo M, Hacein‐Bey S, de Saint Basile G, et al. (2000) Gene therapy of human severe combined immunodeficiency (SCID)‐X1 disease. Science 288: 669–672.

Donahue RE, Kessler SW, Bodine D, et al. (1992) Helper virus induced T cell lymphoma in nonhuman primates after retroviral mediated gene transfer. Journal of Experimental Medicine 176: 1125–1135.

Hacein‐Bey‐Abina S, Le Deist F, Carlier F, et al. (2002) Sustained correction of X‐linked severe combined immunodeficiency by ex vivo gene therapy. New England Journal of Medicine 346: 1185–1193.

Lynch CM, Israel DI, Kaufman RJ and Miller AD (1993) Sequences in the coding region of clotting factor VIII act as dominant inhibitors of RNA accumulation and protein production. Human Gene Therapy 4: 259–272.

Miller AD, Bender MA, Harris EAS, Kaleko M and Gelinas RE (1988) Design of retroviral vectors for transfer and expression of the human β‐globin gene. Journal of Virology 62: 4337–4345.

Miller AD, Miller DG, Garcia JV and Lynch CM (1993) Use of retroviral vectors for gene transfer and expression. Methods in Enzymology 217: 581–599.

Riddell SR, Elliott M, Lewinsohn DA, et al. (1996) T‐cell mediated rejection of gene‐modified HIV‐specific cytotoxic T lymphocytes in HIV‐infected patients. Nature Medicine 2: 216–223.

Vigna E and Naldini L (2000) Lentiviral vectors: excellent tools for experimental gene transfer and promising candidates for gene therapy. Journal of Gene Medicine 2: 308–316.

Further Reading

Coffin JM, Hughes SH and Varmus HE (eds.) (1997) Retroviruses. New York, NY: Cold Spring Harbor Laboratory Press.

Miller DG, Adam MA and Miller AD (1990) Gene transfer by retrovirus vectors occurs only in cells that are actively replicating at the time of infection. Molecular and Cellular Biology 10: 4239–4242.

Web Links

Office of Biotechnology Activities: National Institutes of Health. National Institutes of Health Recombinant DNA Advisory Committes (RAC)‐6_december_02.html

Adenosine deaminase (ADA); Locus ID: 100. LocusLink:

Adenosine deaminase (ADA); MIM number: 102700. OMIM:‐post/Omim/dispmim?102700

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Miller, A Dusty(Jan 2006) Retroviral Vectors in Gene Therapy. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0005741]