学術雑誌論文

学術雑誌論文

Biomolecules. 2024, 14(12), p. 1558

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

Multidisciplinary Digital Publishing Institute (MDPI)

英語

2024-12-06

https://doi.org/10.3390/biom14121558

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.

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.

This article is licensed under a Creative Commons Attribution 4.0 International License.

100430

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

Multidisciplinary Digital Publishing Institute (MDPI)

英語

2024-12-06

Biomolecules

14

12

1558

https://doi.org/10.3390/biom14121558

https://hdl.handle.net/11094/100430