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Infectivity of adeno-associated virus serotypes in mouse testis

Santhanasabapathy Rajasekaran1, Jayashree Thatte1, Jayaprakash Periasamy1

  • 1Institute for Stem Cell Biology and Regenerative Medicine, GKVK Campus, Bellary Road, Bengaluru, 560065, India.

BMC Biotechnology
|November 3, 2018
PubMed
Abstract

Insights

Recombinant adeno-associated viruses (AAVs) show specific tropism in mouse testes, with AAV2 and AAV9 targeting Leydig cells. While generally safe, further assessment of AAV genomic DNA in germ cells is recommended.

Area of Science:

  • Gene therapy
  • Molecular biology
  • Virology

Background:

  • Recombinant adeno-associated viruses (AAVs) are promising vectors for gene therapy and research.
  • Understanding AAV serotype tropism in specific tissues is crucial for effective delivery.
  • The study investigates AAV infectivity in the murine testis.

Purpose of the Study:

  • To evaluate the tropism of various AAV serotypes in the mouse testis following direct injection.
  • To identify specific cell types transduced by different AAV serotypes.
  • To assess the potential of AAVs as gene therapy vectors in the testicular environment.

Main Methods:

  • Direct testicular injection of multiple AAV serotypes (AAV2, 5, 8, 9, AAVrh10) in mice.
  • Analysis of reporter gene expression to determine cell transduction.
  • Comparison of wildtype AAV2 tropism with a modified AAV2 (AAV2 TM) mutant.

Main Results:

  • AAV2 and AAV9 preferentially transduced Leydig cells in the mouse testis.
  • AAV2 TM mutant showed altered tropism, transducing Sertoli cells and infiltrating seminiferous tubules.
  • No tested AAV serotypes infected spermatogonial cells, the sperm progenitors.

Conclusions:

  • The tested AAV serotypes did not infect sperm progenitors, supporting their safety as gene therapy vectors.
  • Further investigation into the presence of rAAV genomic DNA in germ cells is needed to fully assess risks.
  • AAV tropism in the testis is serotype-specific, with potential for targeting specific cell populations like Leydig and Sertoli cells.
Keywords:
Adeno-associated viruses (AAV)Germline transmissionLeydig cellMouse testis injectionMyoid cellSertoli cellSpermatogoniaTropism

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