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Polymeric Nanoparticle Platform Technologies for RNA & Gene Therapeutics
SaxoCell
Nanoparticle
Oncology
Hit To Lead or Lead Optimization
• Therapeutic gene silencing by RNA interference relies on the safe and efficient in vivo delivery of small interfering RNAs (siRNAs). Polyethylenimines are among the most studied cationic polymers for gene delivery.
• For several reasons including superior tolerability, small linear PEIs would be preferable over branched PEIs, but inventors show poor siRNA complexation. Their chemical modification for siRNA formulation has not been extensively explored so far.
• Inventors generated a set of small linear PEIs bearing tyrosine modifications (LPxY), leading to substantially enhanced siRNA delivery and knockdown efficacy in vitro in various cell lines, including hardto-transfect cells. The tyrosine-modified linear 10 kDa PEI (LP10Y) is particularly powerful, associated with favorable physicochemical properties and very high biocompatibility.
• Systemically administered LP10Y/siRNA complexes reveal antitumor effects in mouse xenograft and patient-derived xenograft (PDX) models, and their direct application into the brain achieves therapeutic inhibition of orthotopic glioma xenografts. LP10Y is particularly interesting for therapeutic siRNA delivery.
DE102020114183A1
Tyrosine-modified linear PEIs for highly efficacious and biocompatible siRNA delivery in vitro and in vivo. Nanomedicine: Nanotechnology, Biology and Medicine. (2021)
