Dendritic amphiphilic siRNA: Selective albumin binding, in vivo efficacy, and low toxicity.

ABSTRACT: Although an increasing number of small interfering RNA (siRNA) therapies are reaching the market, the challenge of efficient extra-hepatic delivery continues to limit their full therapeutic potential. Drug delivery vehicles and hydrophobic conjugates are being used to overcome the delivery bottleneck. Previously, we reported a novel dendritic conjugate that can be appended efficiently to oligonucleotides, allowing them to bind albumin with nanomolar affinity. Here, we explore the ability of this novel albumin-binding conjugate to improve the delivery of siRNA in vivo. We demonstrate that the conjugate binds albumin exclusively in circulation and extravasates to various organs, enabling effective gene silencing. Notably, we show that the conjugate achieves a balance between hydrophob

SUBMITTER: Fakih HH 

PROVIDER: S-EPMC10711485 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature