A ribonucleoprotein octamer for targeted siRNA delivery

Area of Science:

• Biotechnology
• Nanomedicine
• Molecular Biology

Background:

• Cell-specific delivery of small interfering RNA (siRNA) for RNA interference (RNAi) therapies faces significant hurdles in clinical translation.
• Existing delivery vehicles often present conflicting properties, such as facilitating endosomal escape but compromising in vivo targeting and stability.

Purpose of the Study:

• To engineer a novel nanoparticle for efficient and targeted in vivo delivery of siRNA.
• To overcome the limitations of current delivery systems for RNAi therapeutics.

Main Methods:

• Development of a self-assembled, biocompatible ribonucleoprotein-octamer nanoparticle (~30 nm).
• Incorporation of a poly(ethylene glycol) scaffold, an endosomolytic peptide, and a double-stranded RNA-binding domain.
• Functionalization with a targeting ligand for prostate-specific membrane antigen (PSMA).

Main Results:

• The nanoparticle demonstrated efficient siRNA loading (>30 wt%) and endosomal destabilization.
• Targeted gene silencing of polo-like kinase 1 (PLK1) was achieved in prostate cancer cells in vitro.
• Effective in vivo gene silencing was observed in mouse models of prostate cancer following intravenous injection.

Conclusions:

• The developed ribonucleoprotein-octamer nanoparticle is a versatile nanocarrier for intracellularly acting biologics.
• This platform offers a promising strategy for advancing RNAi-based therapies towards clinical application.