Enhancement of Gene Editing and Base Editing with Therapeutic Ribonucleoproteins through In Vivo Delivery Based on Absorptive Silica Nanoconstruct

Seongchan Kim, You Kyeong Jeong, Chang Sik Cho, Seok Hoon Lee, Chang Ho Sohn, Jeong Hun Kim, Youngdo Jeong, Dong Hyun Jo, Sangsu Bae, Hyojin Lee

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Key to the widespread and secure application of genome editing tools is the safe and effective delivery of multiple components of ribonucleoproteins (RNPs) into single cells, which remains a biological barrier to their clinical application. To overcome this issue, a robust RNP delivery platform based on a biocompatible sponge-like silica nanoconstruct (SN) for storing and directly delivering therapeutic RNPs, including Cas9 nuclease RNP (Cas9-RNP) and base editor RNP (BE-RNP) is designed. Compared with commercialized material such as lipid-based methods, up to 50-fold gene deletion and 10-fold base substitution efficiency is obtained with a low off-target efficiency by targeting various cells and genes. In particular, gene correction is successfully induced by SN-based delivery through intravenous injection in an in vivo solid-tumor model and through subretinal injection in mouse eye. Moreover, because of its low toxicity and high biodegradability, SN has negligible effect on cellular function of organs. As the engineered SN can overcome practical challenges associated with therapeutic RNP application, it is strongly expected this platform to be a modular RNPs delivery system, facilitating in vivo gene deletion and editing.

Original languageEnglish
Article number2201825
JournalAdvanced Healthcare Materials
Volume12
Issue number4
DOIs
Publication statusPublished - 2023 Feb 6

Bibliographical note

Publisher Copyright:
© 2022 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.

All Science Journal Classification (ASJC) codes

  • Biomaterials
  • Biomedical Engineering
  • Pharmaceutical Science

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