Lipid Nanoparticles Enable Efficient In Vivo DNA Knock-In via HITI-Mediated Genome Editing

Hirose, Jun; Aizawa, Emi; Yamamoto, Shogo et al.

Biomolecules, 2024, 14(12), 1558

Number of Access:504（2025-09-03 11:41 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/100430

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Title
Lipid Nanoparticles Enable Efficient In Vivo DNA Knock-In via HITI-Mediated Genome Editing
Creator
CreatorName
Hirose, Jun
CreatorName
Aizawa, Emi
CreatorName
Yamamoto, Shogo
CreatorName
Xu, Mingyao
NRID
1000010168544 1000010168544
researchmap permalink
read0076907 read0076907
Scopus Author ID
7201640584 7201640584
CreatorName
Iwai, Shigenori
NRID
1000070433654 1000070433654
ORCID
0000-0001-5603-9105 0000-0001-5603-9105
researchmap permalink
ksuzuki ksuzuki
Scopus Author ID
55389105500 55389105500
CreatorName
Suzuki, Keiichiro
Subject
genome editing
homology-independent targeted integration (HITI)
knock-in
lipid nanoparticle (LNP)
Description
Hirose J., Aizawa E., Yamamoto S., et al. Lipid Nanoparticles Enable Efficient In Vivo DNA Knock-In via HITI-Mediated Genome Editing. Biomolecules 14, 1558 (2024); https://doi.org/10.3390/biom14121558.
Abstract
In vivo genome editing holds great therapeutic potential for treating monogenic diseases by enabling precise gene correction or addition. However, improving the efficiency of delivery systems remains a key challenge. In this study, we investigated the use of lipid nanoparticles (LNPs) for in vivo knock-in of ectopic DNA. Our in vitro experiments demonstrated that the homology-independent targeted integration (HITI)-mediated genome-editing method achieved significantly higher knock-in efficiency at the Alb locus in hepatic cells compared to the traditional homology-directed repair (HDR)-mediated approach. By optimizing LNP composition and administration routes, we successfully achieved HITI-mediated GFP knock-in (2.1–2.7%) in the livers of mice through intravenous delivery of LNP-loaded genome editing components. Notably, repeated intravenous dosing led to a twofold increase in liver GFP knock-in efficiency (4.3–7.0%) compared to a single dose, highlighting the potential for cumulative genome editing effects. These findings provide a solid foundation for the use of LNPs in in vivo knock-in strategies, paving the way for future genome-editing therapies.
Publisher
Multidisciplinary Digital Publishing Institute (MDPI)
Source Title
Biomolecules
Volume (Issue)
14(12)
Page
1558
Date of Issued
2024-12-06
Language
English
Handle URL
https://hdl.handle.net/11094/100430
eISSN
2218273X
Relation.isIdenticalTo
DOI (Publisher Version)
https://doi.org/10.3390/biom14121558
Access Rights
open access
CopyRight
This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version
Version of Record
Category
学術雑誌論文 Journal Article