Bibliographic Details
| Title: |
Lipid Nanoparticles Enable Efficient In Vivo DNA Knock-In via HITI-Mediated Genome Editing |
| Authors: |
Jun Hirose, Emi Aizawa, Shogo Yamamoto, Mingyao Xu, Shigenori Iwai, Keiichiro Suzuki |
| Source: |
Biomolecules, Vol 14, Iss 12, p 1558 (2024) |
| Publisher Information: |
MDPI AG, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Microbiology |
| Subject Terms: |
genome editing, lipid nanoparticle (LNP), homology-independent targeted integration (HITI), knock-in, Microbiology, QR1-502 |
| More Details: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2218-273X |
| Relation: |
https://www.mdpi.com/2218-273X/14/12/1558; https://doaj.org/toc/2218-273X |
| DOI: |
10.3390/biom14121558 |
| Access URL: |
https://doaj.org/article/198dd1759f3e48fba1700157a0a51797 |
| Accession Number: |
edsdoj.198dd1759f3e48fba1700157a0a51797 |
| Database: |
Directory of Open Access Journals |
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