Cellular immunity to viral antigens limits E1-deleted adenoviruses for gene therapy - PubMed (original) (raw)
Comparative Study
Cellular immunity to viral antigens limits E1-deleted adenoviruses for gene therapy
Y Yang et al. Proc Natl Acad Sci U S A. 1994.
Abstract
An important limitation that has emerged in the use of adenoviruses for gene therapy has been loss of recombinant gene expression that occurs concurrent with the development of pathology in the organ expressing the transgene. We have used liver-directed approaches to gene therapy in mice to study mechanisms that underlie the problems with transient expression and pathology that have characterized in vivo applications of first-generation recombinant adenoviruses (i.e., those deleted of E1a and E1b). Our data are consistent with the following hypothesis. Cells harboring the recombinant viral genome express the transgene as desired; however, low-level expression of viral genes also occurs. A virus-specific cellular immune response is stimulated that leads to destruction of the genetically modified hepatocytes, massive hepatitis, and repopulation of the liver with nontransgene-containing hepatocytes. These findings suggest approaches for improving recombinant adenoviruses that are based on further crippling the virus to limit expression of nondeleted viral genes.
Similar articles
- Prolonged transgene expression in cotton rat lung with recombinant adenoviruses defective in E2a.
Engelhardt JF, Litzky L, Wilson JM. Engelhardt JF, et al. Hum Gene Ther. 1994 Oct;5(10):1217-29. doi: 10.1089/hum.1994.5.10-1217. Hum Gene Ther. 1994. PMID: 7849095 - Ablation of E2A in recombinant adenoviruses improves transgene persistence and decreases inflammatory response in mouse liver.
Engelhardt JF, Ye X, Doranz B, Wilson JM. Engelhardt JF, et al. Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):6196-200. doi: 10.1073/pnas.91.13.6196. Proc Natl Acad Sci U S A. 1994. PMID: 8016137 Free PMC article. - Mutant adenoviruses selectively replication-competent in tumor cells.
Sunamura M. Sunamura M. Adv Exp Med Biol. 2000;465:65-71. doi: 10.1007/0-306-46817-4_7. Adv Exp Med Biol. 2000. PMID: 10810616 Review. No abstract available. - Immune responses to adenoviruses: viral evasion mechanisms and their implications for the clinic.
Wold WS, Doronin K, Toth K, Kuppuswamy M, Lichtenstein DL, Tollefson AE. Wold WS, et al. Curr Opin Immunol. 1999 Aug;11(4):380-6. doi: 10.1016/S0952-7915(99)80064-8. Curr Opin Immunol. 1999. PMID: 10448144 Review.
Cited by
- SARS-CoV-2 vaccine ChAdOx1 nCoV-19 infection of human cell lines reveals low levels of viral backbone gene transcription alongside very high levels of SARS-CoV-2 S glycoprotein gene transcription.
Almuqrin A, Davidson AD, Williamson MK, Lewis PA, Heesom KJ, Morris S, Gilbert SC, Matthews DA. Almuqrin A, et al. Genome Med. 2021 Mar 15;13(1):43. doi: 10.1186/s13073-021-00859-1. Genome Med. 2021. PMID: 33722288 Free PMC article. - (2-Hydroxypropyl)-β-Cyclodextrin Is a New Angiogenic Molecule for Therapeutic Angiogenesis.
Qi X, Yuan Y, Xu K, Zhong H, Zhang Z, Zhai H, Guan G, Yu G. Qi X, et al. PLoS One. 2015 May 5;10(5):e0125323. doi: 10.1371/journal.pone.0125323. eCollection 2015. PLoS One. 2015. PMID: 25944736 Free PMC article. - Pulmonary immunity to viral infection: adenovirus infection of lung dendritic cells renders T cells nonresponsive to interleukin-2.
Thiele AT, Sumpter TL, Walker JA, Xu Q, Chang CH, Bacallao RL, Kher R, Wilkes DS. Thiele AT, et al. J Virol. 2006 Feb;80(4):1826-36. doi: 10.1128/JVI.80.4.1826-1836.2006. J Virol. 2006. PMID: 16439539 Free PMC article. - Gene therapy of bone morphogenetic protein for periodontal tissue engineering.
Jin QM, Anusaksathien O, Webb SA, Rutherford RB, Giannobile WV. Jin QM, et al. J Periodontol. 2003 Feb;74(2):202-13. doi: 10.1902/jop.2003.74.2.202. J Periodontol. 2003. PMID: 12666709 Free PMC article. - An adenovirus type 5 (Ad5) amplicon-based packaging cell line for production of high-capacity helper-independent deltaE1-E2-E3-E4 Ad5 vectors.
Catalucci D, Sporeno E, Cirillo A, Ciliberto G, Nicosia A, Colloca S. Catalucci D, et al. J Virol. 2005 May;79(10):6400-9. doi: 10.1128/JVI.79.10.6400-6409.2005. J Virol. 2005. PMID: 15858023 Free PMC article.
References
- J Gen Virol. 1977 Jul;36(1):59-74 - PubMed
- Hum Gene Ther. 1993 Dec;4(6):771-80 - PubMed
- Virology. 1983 Jul 30;128(2):480-4 - PubMed
- Mol Cell Biol. 1984 May;4(5):867-74 - PubMed
- Anal Biochem. 1987 Apr;162(1):156-9 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical