Dataset Information

Liver-specific in vivo base editing of Angptl3 via AAV delivery efficiently lowers blood lipid levels in mice.

ABSTRACT:

Background

Gene editing has emerged as an exciting therapeutic development platform for numerous genetic and nongenetic diseases. Targeting lipid-modulating genes such as angiopoietin-related protein 3 (ANGPTL3) with gene editing offers hope for a permanent solution to lower cardiovascular disease risks associated with hypercholesterolemia.

Results

In this study, we developed a hepatocyte-specific base editing therapeutic approach delivered by dual adeno-associated virus (AAV) to enable hepatocyte-specific targeting of Angptl3 to lower blood lipid levels. Systemic AAV9-mediated delivery of AncBE4max, a cytosine base editor (CBE), targeting mouse Angptl3 resulted in the installation of a premature stop codon in Angptl3 with an average efficiency of 63.3 ± 2.3% in the bulk liver tissue. A near-complete knockout of the ANGPTL3 protein in the circulation were observed within 2-4 weeks following AAV administration. Furthermore, the serum levels of triglyceride (TG) and total cholesterol (TC) were decreased by approximately 58% and 61%, respectively, at 4 weeks after treatment.

Conclusions

These results highlight the promise of liver-targeted Angptl3 base editing for blood lipid control.

SUBMITTER: Zuo Y

PROVIDER: S-EPMC10273718 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Publications

Liver-specific in vivo base editing of Angptl3 via AAV delivery efficiently lowers blood lipid levels in mice.

Zuo Yuanbojiao Y Zhang Chen C Zhou Yuan Y Li Haiwen H Xiao Weidong W Herzog Roland W RW Xu Jie J Zhang Jifeng J Chen Y Eugene YE Han Renzhi R

Cell & bioscience 20230615 1

<h4>Background</h4>Gene editing has emerged as an exciting therapeutic development platform for numerous genetic and nongenetic diseases. Targeting lipid-modulating genes such as angiopoietin-related protein 3 (ANGPTL3) with gene editing offers hope for a permanent solution to lower cardiovascular disease risks associated with hypercholesterolemia.<h4>Results</h4>In this study, we developed a hepatocyte-specific base editing therapeutic approach delivered by dual adeno-associated virus (AAV) to ...[more]

PMID: 37322547

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Dataset Information

Liver-specific in vivo base editing of Angptl3 via AAV delivery efficiently lowers blood lipid levels in mice.

Background

Results

Conclusions

Publications

Liver-specific in vivo base editing of Angptl3 via AAV delivery efficiently lowers blood lipid levels in mice.

Similar Datasets

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