Infectivity of adeno-associated virus serotypes in mouse testis |
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Authors: | Santhanasabapathy Rajasekaran Jayashree Thatte Jayaprakash Periasamy Alok Javali Manjunath Jayaram Dwaipayan Sen Akshaya Krishnagopal Giridhara R Jayandharan Ramkumar Sambasivan |
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Institution: | 1.Institute for Stem Cell Biology and Regenerative Medicine,GKVK Campus,Bengaluru,India;2.National Centre for Biological Sciences,TIFR, GKVK Campus,Bengaluru,India;3.Department of Haematology and Centre for Stem Cell Research,Christian Medical College,Vellore,India;4.Cellular and Molecular Therapeutics Laboratory, Centre for Biomaterials, Cellular and Molecular Theranostics (CBCMT),Vellore Institute of Technology (VIT),Vellore,India;5.Department of Biological Sciences and Bioengineering,Indian Institute of Technology,Kanpur,India |
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Abstract: | BackgroundRecombinant 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.ResultsWe 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.ConclusionsIn 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. |
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