AAV-DJ Enables Targeted Gene Modulation in Human Ovarian Cells
Study question: Can adeno-associated viruses (AAVs) efficiently and safely transduce human primary granulosa cells and human ovarian stromal fibroblasts to modulate the expression of genes involved in follicle recruitment and ovarian microenvironment regulation? Summary answer: AAVs can efficiently transduce human primary granulosa cells and human ovarian stromal cells with low toxicity, with the…
A study investigates whether adeno-associated viruses (AAVs) can efficiently and safely modify genes in human ovarian cells to improve fertility. Researchers explored 16 different AAV serotypes for their ability to infect and modify human primary granulosa cells and ovarian stromal fibroblasts, which are key components of the ovarian microenvironment.
The research found that AAVs were able to efficiently infect human primary granulosa cells and ovarian stromal cells without causing significant toxicity. Among the tested serotypes, AAV-DJ showed the highest transduction efficiency, reaching up to 48% at a high multiplicity of infection. Despite potential toxicity increases with higher viral doses, AAV-DJ maintained its efficiency with only moderate toxicity.
The scientists then used AAV-DJ to target specific genes involved in ovarian function. In human primary granulosa cells, AAV-DJ-mediated shRNA knockdown of the AMHR2 gene resulted in an 81% reduction in AMHR2 mRNA levels. In ovarian stromal cells, AAV-DJ-mediated knockdown of the TGF-β1 gene showed a reduction in TGF-β1 protein expression.
These findings demonstrate that AAV-DJ can effectively and safely modulate gene expression in human ovarian cells, paving the way for potential gene-based therapies to improve ovarian function in women with infertility issues.
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