Journal
GENE THERAPY
Volume 17, Issue 3, Pages 295-304Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/gt.2009.148
Keywords
innate immunity; adaptive immunity; adeno-associated virus; lentivirus; adenovirus; immune modulation
Categories
Funding
- NIH [P01 HL078810, R01 AI/HL51390, T32DK074367]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [P01HL078810] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI051390] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [T32DK074367] Funding Source: NIH RePORTER
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Viral vectors are potent gene delivery platforms used for the treatment of genetic and acquired diseases. However, just as viruses have evolved to infect cells efficiently, the immune system has evolved to fight off what it perceives as invading pathogens. Therefore, innate immunity and antigen-specific adaptive immune responses against vector-derived antigens reduce the efficacy and stability of in vivo gene transfer. In addition, a number of vectors are derived from parent viruses that humans encounter through natural infection, resulting in preexisting antibodies and possibly in memory responses against vector antigens. Similarly, antibody and T-cell responses may be directed against therapeutic gene products that often differ from the endogenous nonfunctional or absent protein that is being replaced. As details and mechanisms of such immune reactions are uncovered, novel strategies are being developed, and vectors are being specifically engineered to avoid, suppress or manipulate the response, ideally resulting in sustained expression and immune tolerance to the transgene product. This review provides a summary of our current knowledge of the interactions between the immune system adeno-associated virus, adenoviral and lentiviral vectors, and their transgene products. Gene Therapy (2010) 17, 295-304; doi:10.1038/gt.2009.148; published online 12 November 2009
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