TitleInfectivity of adeno-associated virus serotypes in mouse testis.
Publication TypeJournal Article
Year of Publication2018
AuthorsRajasekaran S, Thatte J, Periasamy J, Javali A, Jayaram M, Sen D, Krishnagopal A, Jayandharan GR, Sambasivan R
JournalBMC Biotechnol
Volume18
Issue1
Pagination70
Date Published2018 Nov 01
ISSN1472-6750
Abstract

BACKGROUND: Recombinant adeno-associated viruses (AAVs) are emerging as favoured transgene delivery vectors for both research applications and gene therapy. In this context, a thorough investigation of the potential of various AAV serotypes to transduce specific cell types is valuable. Here, we rigorously tested the infectivity of a number of AAV serotypes in murine testis by direct testicular injection.

RESULTS: We report the tropism of serotypes AAV2, 5, 8, 9 and AAVrh10 in mouse testis. We reveal unique infectivity of AAV2 and AAV9, which preferentially target intertubular testosterone-producing Leydig cells. Remarkably, AAV2 TM, a mutant for capsid designed to increase transduction, displayed a dramatic alteration in tropism; it infiltrated seminiferous tubules unlike wildtype AAV2 and transduced Sertoli cells. However, none of the AAVs tested infected spermatogonial cells.

CONCLUSIONS: In spite of direct testicular injection, none of the tested AAVs appeared to infect sperm progenitors as assayed by reporter expression. This lends support to the current view that AAVs are safe gene-therapy vehicles. However, testing the presence of rAAV genomic DNA in germ cells is necessary to assess the risk of individual serotypes.

DOI10.1186/s12896-018-0479-1
Alternate JournalBMC Biotechnol.
PubMed ID30384832
PubMed Central IDPMC6211462
Grant ListBT/RLF/Re-entry/03/2010 / / Department of Biotechnology , Ministry of Science and Technology /
BT/PR5981/MED/31/181/2012;2013-2016 / / Department of Biotechnology , Ministry of Science and Technology /