PMID- 36326169
OWN - NLM
STAT- MEDLINE
DCOM- 20230216
LR  - 20230227
IS  - 2192-2659 (Electronic)
IS  - 2192-2640 (Linking)
VI  - 12
IP  - 4
DP  - 2023 Feb
TI  - Enhancement of Gene Editing and Base Editing with Therapeutic Ribonucleoproteins 
      through In Vivo Delivery Based on Absorptive Silica Nanoconstruct.
PG  - e2201825
LID - 10.1002/adhm.202201825 [doi]
AB  - 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.
CI  - (c) 2022 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.
FAU - Kim, Seongchan
AU  - Kim S
AD  - Biomaterials Research Center, Biomedical Research Institute, Korea Institute of 
      Science and Technology (KIST), 02792, Seoul, Republic of Korea.
FAU - Jeong, You Kyeong
AU  - Jeong YK
AD  - Medical Research Center of Genomic Medicine Institute, Seoul National University 
      College of Medicine, 03080, Seoul, Republic of Korea.
FAU - Cho, Chang Sik
AU  - Cho CS
AD  - Fight Against Angiogenesis-Related Blindness (FARB) Laboratory, Biomedical 
      Research Institute, Seoul National University Hospital, 03080, Seoul, Republic of 
      Korea.
FAU - Lee, SeokHoon
AU  - Lee S
AD  - Department of Biomedical Sciences, Seoul National University College of Medicine, 
      03080, Seoul, Republic of Korea.
FAU - Sohn, Chang Ho
AU  - Sohn CH
AD  - Center for Nanomedicine, Institute for Basic Science, Graduate Program in 
      Nanobiomedical Engineering, Advanced Science Institute, Yonsei University, 03722, 
      Seoul, Republic of Korea.
FAU - Kim, Jeong Hun
AU  - Kim JH
AD  - Fight Against Angiogenesis-Related Blindness (FARB) Laboratory, Biomedical 
      Research Institute, Seoul National University Hospital, 03080, Seoul, Republic of 
      Korea.
AD  - Department of Ophthalmology and Department of Biomedical Sciences, Seoul National 
      University College of Medicine, 03080, Seoul, Republic of Korea.
FAU - Jeong, Youngdo
AU  - Jeong Y
AD  - Biomaterials Research Center, Biomedical Research Institute, Korea Institute of 
      Science and Technology (KIST), 02792, Seoul, Republic of Korea.
FAU - Jo, Dong Hyun
AU  - Jo DH
AD  - Department of Anatomy and Cell Biology, Seoul National University College of 
      Medicine, 03080, Seoul, Republic of Korea.
FAU - Bae, Sangsu
AU  - Bae S
AD  - Medical Research Center of Genomic Medicine Institute, Seoul National University 
      College of Medicine, 03080, Seoul, Republic of Korea.
AD  - Department of Biomedical Sciences, Seoul National University College of Medicine, 
      03080, Seoul, Republic of Korea.
FAU - Lee, Hyojin
AU  - Lee H
AUID- ORCID: 0000-0001-6367-9485
AD  - Biomaterials Research Center, Biomedical Research Institute, Korea Institute of 
      Science and Technology (KIST), 02792, Seoul, Republic of Korea.
AD  - Division of Bio-Medical Science & Technology, KIST School - Korea University of 
      Science and Technology (UST), 02792, Seoul, Republic of Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221110
PL  - Germany
TA  - Adv Healthc Mater
JT  - Advanced healthcare materials
JID - 101581613
RN  - 0 (Ribonucleoproteins)
RN  - 7631-86-9 (Silicon Dioxide)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *CRISPR-Cas Systems/genetics
MH  - *Gene Editing/methods
MH  - Genetic Therapy
MH  - *Ribonucleoproteins/genetics/metabolism
MH  - Nanostructures/administration & dosage
MH  - *Silicon Dioxide/administration & dosage/pharmacology
OTO - NOTNLM
OT  - base editing
OT  - gene editing
OT  - porous nanoparticles
OT  - ribonucleoproteins delivery
OT  - targeted tumor therapy
EDAT- 2022/11/04 06:00
MHDA- 2023/02/08 06:00
CRDT- 2022/11/03 08:03
PHST- 2022/10/31 00:00 [revised]
PHST- 2022/07/22 00:00 [received]
PHST- 2022/11/04 06:00 [pubmed]
PHST- 2023/02/08 06:00 [medline]
PHST- 2022/11/03 08:03 [entrez]
AID - 10.1002/adhm.202201825 [doi]
PST - ppublish
SO  - Adv Healthc Mater. 2023 Feb;12(4):e2201825. doi: 10.1002/adhm.202201825. Epub 
      2022 Nov 10.