Development of a Modular Ribonucleoprotein Complex as a General Strategy to Deliver RNAi Therapeutics.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40702844.
- Also identified by DOI 10.1002/adhm.202503281 and PMC identifier 12477566.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
RNAi therapeutics can potentially address undruggable diseases. However, their full potential is stymied by delivery challenges. An siRNA delivery platform by remodeling the human U4 small nuclear ribonucleoprotein complex (snRNP) is developed. This remodeled protein-siRNA complex (SmiRNP) serves as a biocompatible, modular, and customizable platform for attaching desired functional modules to overcome delivery hurdles. Here, it is demonstrated that the SmiRNP complex, by using siRNA against KRAS as a proof of principle, can deliver the siRNA into cells and protect it from nuclease degradation, allowing the siRNA to knockdown KRAS mRNA and protein levels, reduce cancer cell viability, and suppress tumor growth in vivo. This general strategy allows many more modular combinations and would enable the delivery of a wide spectrum of RNAi therapeutics.
Medical subject headings
- RNA, Small Interfering
- RNAi Therapeutics
- Ribonucleoproteins
- Ribonucleoproteins, Small Nuclear