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Effect of viral dose on neutralizing antibody response and transgene expression after AAV1 vector re-administration in mice.
Gene Ther 2008; 15(1):54-60GT

Abstract

Neutralizing antibodies (nAB) at the time of administration hamper the effectiveness of adeno-associated virus (AAV) as a clinical DNA delivery system. The present study was designed to investigate if AAV re-administration in muscle tissue is dependent on the nAB titer. Recombinant (r)AAV serotype 1, as a promising candidate for targeting skeletal muscle, was used for gene delivery. C57Bl/6 mice were infected intramuscularly with doses between 1 x 10(9) and 5 x 10(10) virus particles (vp) of AAV1-expressing luciferase (AAV1-luc) or human interferon-beta (AAV1-hIFNbeta). Increasing transgene expression was observed over the first 2 months and anti-AAV1 nAB titers peaked between weeks 4 and 8. Six months after the first administration, 5 x 10(10) vp of AAV1-IFNbeta were re-administered. Following re-administration, nAB titers increased but did not significantly affect transgene expression from the AAV vector that had been administered first. In contrast, hIFNbeta expression originating from the second vector administration was significantly diminished and reflected the nAB titer present at the day of re-administration. The present study extends earlier observations that preexisting nAB affects AAV1 re-administration. The level of nAB is proportional to the virus dose used for the first injection and transgene expression following re-administration is dependent on preexisting nAB titer.

Authors+Show Affiliations

Department of Gene Technologies, Berlex Biosciences, Richmond, CA, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17960164

Citation

Petry, H, et al. "Effect of Viral Dose On Neutralizing Antibody Response and Transgene Expression After AAV1 Vector Re-administration in Mice." Gene Therapy, vol. 15, no. 1, 2008, pp. 54-60.
Petry H, Brooks A, Orme A, et al. Effect of viral dose on neutralizing antibody response and transgene expression after AAV1 vector re-administration in mice. Gene Ther. 2008;15(1):54-60.
Petry, H., Brooks, A., Orme, A., Wang, P., Liu, P., Xie, J., ... Harkins, R. N. (2008). Effect of viral dose on neutralizing antibody response and transgene expression after AAV1 vector re-administration in mice. Gene Therapy, 15(1), pp. 54-60.
Petry H, et al. Effect of Viral Dose On Neutralizing Antibody Response and Transgene Expression After AAV1 Vector Re-administration in Mice. Gene Ther. 2008;15(1):54-60. PubMed PMID: 17960164.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of viral dose on neutralizing antibody response and transgene expression after AAV1 vector re-administration in mice. AU - Petry,H, AU - Brooks,A, AU - Orme,A, AU - Wang,P, AU - Liu,P, AU - Xie,J, AU - Kretschmer,P, AU - Qian,H S, AU - Hermiston,T W, AU - Harkins,R N, Y1 - 2007/10/25/ PY - 2007/10/26/pubmed PY - 2008/4/12/medline PY - 2007/10/26/entrez SP - 54 EP - 60 JF - Gene therapy JO - Gene Ther. VL - 15 IS - 1 N2 - Neutralizing antibodies (nAB) at the time of administration hamper the effectiveness of adeno-associated virus (AAV) as a clinical DNA delivery system. The present study was designed to investigate if AAV re-administration in muscle tissue is dependent on the nAB titer. Recombinant (r)AAV serotype 1, as a promising candidate for targeting skeletal muscle, was used for gene delivery. C57Bl/6 mice were infected intramuscularly with doses between 1 x 10(9) and 5 x 10(10) virus particles (vp) of AAV1-expressing luciferase (AAV1-luc) or human interferon-beta (AAV1-hIFNbeta). Increasing transgene expression was observed over the first 2 months and anti-AAV1 nAB titers peaked between weeks 4 and 8. Six months after the first administration, 5 x 10(10) vp of AAV1-IFNbeta were re-administered. Following re-administration, nAB titers increased but did not significantly affect transgene expression from the AAV vector that had been administered first. In contrast, hIFNbeta expression originating from the second vector administration was significantly diminished and reflected the nAB titer present at the day of re-administration. The present study extends earlier observations that preexisting nAB affects AAV1 re-administration. The level of nAB is proportional to the virus dose used for the first injection and transgene expression following re-administration is dependent on preexisting nAB titer. SN - 1476-5462 UR - https://www.unboundmedicine.com/medline/citation/17960164/Effect_of_viral_dose_on_neutralizing_antibody_response_and_transgene_expression_after_AAV1_vector_re_administration_in_mice_ L2 - http://dx.doi.org/10.1038/sj.gt.3303037 DB - PRIME DP - Unbound Medicine ER -