CAP 2 is an ionizable cationic lipid composed of two cholesterol units connected by a phosphate linker with an amino head group. It has been utilized in the development of lipid nanoparticles (LNPs) for the in vivo delivery of mRNA or self-amplifying RNA (saRNA). LNPs containing CAP 2 and encapsulating saRNA encoding DNA meiotic recombinase 1 (Dmc1) sustain elevated Dmc1 levels in seminiferous tubules for longer durations compared to LNPs with Dmc1 mRNA in a Dmc1-/- mouse model of male infertility. These saRNA-loaded LNPs also enhance the percentage of morphologically mature spermatocytes, increase the thickness of the germinal layer, and enlarge the diameter of seminiferous tubules. Additionally, sperm from treated mice successfully fertilized mouse oocytes, resulting in viable embryos.
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