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Current strategies and future directions for eluding adenoviral vector immunity.
Curr Gene Ther. 2006 Apr; 6(2):215-26.CG

Abstract

Adenoviral (Ad) vectors can efficiently transduce a broad range of cell types and have been used extensively in preclinical and clinical studies for gene delivery applications. The presence of preexisting Ad immunity in the majority of human population and a rapid development of immune response against the Ad vector backbone following the first inoculation with the vector have impeded clinical use of these vectors. In addition, a number of animal inoculation studies have demonstrated that high systemic doses of Ad vectors invariably lead to initiation of acute inflammatory responses. This is mainly due to activation of innate immunity by vector particles. In general, vector and innate immune responses drastically limit the vector transduction efficiency and the duration of transgene expression. In order to have a predictable response with Ad vectors for gene therapy applications, the above limitations must be overcome. Strategies that are being examined to circumvent these drawbacks of Ad vectors include immunosuppression, immunomodulation, serotype switching, use of targeted Ad vectors, microencapsulation of Ad vectors, use of helper-dependent (HD) Ad vectors, and development of nonhuman Ad vectors. Here we review the current understanding of immune responses to Ad vectors, and recent advances in the strategies for immune evasion to improve the vector transduction efficiency and the duration of transgene expression. Development of novel strategies for targeting specific cell types would further boost the utility of Ad vectors by enhancing the safety, efficacy and duration of transgene expression.

Authors+Show Affiliations

Laboratory of Gene Therapy, Department of Pathobiology and Purdue Cancer Center, Purdue University, West Lafayette, IN 47907, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Review

Language

eng

PubMed ID

16611043

Citation

Bangari, Dinesh S., and Suresh K. Mittal. "Current Strategies and Future Directions for Eluding Adenoviral Vector Immunity." Current Gene Therapy, vol. 6, no. 2, 2006, pp. 215-26.
Bangari DS, Mittal SK. Current strategies and future directions for eluding adenoviral vector immunity. Curr Gene Ther. 2006;6(2):215-26.
Bangari, D. S., & Mittal, S. K. (2006). Current strategies and future directions for eluding adenoviral vector immunity. Current Gene Therapy, 6(2), 215-26.
Bangari DS, Mittal SK. Current Strategies and Future Directions for Eluding Adenoviral Vector Immunity. Curr Gene Ther. 2006;6(2):215-26. PubMed PMID: 16611043.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Current strategies and future directions for eluding adenoviral vector immunity. AU - Bangari,Dinesh S, AU - Mittal,Suresh K, PY - 2006/4/14/pubmed PY - 2006/7/28/medline PY - 2006/4/14/entrez SP - 215 EP - 26 JF - Current gene therapy JO - Curr Gene Ther VL - 6 IS - 2 N2 - Adenoviral (Ad) vectors can efficiently transduce a broad range of cell types and have been used extensively in preclinical and clinical studies for gene delivery applications. The presence of preexisting Ad immunity in the majority of human population and a rapid development of immune response against the Ad vector backbone following the first inoculation with the vector have impeded clinical use of these vectors. In addition, a number of animal inoculation studies have demonstrated that high systemic doses of Ad vectors invariably lead to initiation of acute inflammatory responses. This is mainly due to activation of innate immunity by vector particles. In general, vector and innate immune responses drastically limit the vector transduction efficiency and the duration of transgene expression. In order to have a predictable response with Ad vectors for gene therapy applications, the above limitations must be overcome. Strategies that are being examined to circumvent these drawbacks of Ad vectors include immunosuppression, immunomodulation, serotype switching, use of targeted Ad vectors, microencapsulation of Ad vectors, use of helper-dependent (HD) Ad vectors, and development of nonhuman Ad vectors. Here we review the current understanding of immune responses to Ad vectors, and recent advances in the strategies for immune evasion to improve the vector transduction efficiency and the duration of transgene expression. Development of novel strategies for targeting specific cell types would further boost the utility of Ad vectors by enhancing the safety, efficacy and duration of transgene expression. SN - 1566-5232 UR - https://www.unboundmedicine.com/medline/citation/16611043/Current_strategies_and_future_directions_for_eluding_adenoviral_vector_immunity_ L2 - https://www.eurekaselect.com/55570/article DB - PRIME DP - Unbound Medicine ER -