Widespread Gene Editing in the Brain via In Utero Delivery of mRNA Using Acid-Degradable Lipid Nanoparticles DOI Creative Commons
Kewa Gao, Hesong Han,

Matileen Grace Cranick

и другие.

ACS Nano, Год журнала: 2024, Номер 18(44), С. 30293 - 30306

Опубликована: Окт. 24, 2024

In utero gene editing with mRNA-based therapeutics has the potential to revolutionize treatment of neurodevelopmental disorders. However, a critical bottleneck in clinical application been lack mRNA delivery vehicles that can efficiently transfect cells brain. this report, we demonstrate intracerebroventricular (ICV) injection densely PEGylated lipid nanoparticles (ADP-LNPs) containing an acid-degradable PEG–lipid safely and effectively deliver for enzymes fetal mouse brain, resulting successful transfection brain cells. ADP-LNPs Cre transfected 30% Ai9 mice had no detectable adverse effects on development postnatal growth. addition, neural stem progenitor mRNA, which subsequently proliferated caused over 40% cortical neurons 60% hippocampal be edited treated 10 weeks after birth. Furthermore, using Angelman syndrome, paradigmatic disorder, as disease model, carrying Cas9 gRNA induced indels 21% within 7 days postpartum, underscoring precision approach. These findings LNP/mRNA complexes have transformative tool disorders set stage frontier treating focuses curing genetic diseases before

Язык: Английский

Widespread Gene Editing in the Brain via In Utero Delivery of mRNA Using Acid-Degradable Lipid Nanoparticles DOI Creative Commons
Kewa Gao, Hesong Han,

Matileen Grace Cranick

и другие.

ACS Nano, Год журнала: 2024, Номер 18(44), С. 30293 - 30306

Опубликована: Окт. 24, 2024

In utero gene editing with mRNA-based therapeutics has the potential to revolutionize treatment of neurodevelopmental disorders. However, a critical bottleneck in clinical application been lack mRNA delivery vehicles that can efficiently transfect cells brain. this report, we demonstrate intracerebroventricular (ICV) injection densely PEGylated lipid nanoparticles (ADP-LNPs) containing an acid-degradable PEG–lipid safely and effectively deliver for enzymes fetal mouse brain, resulting successful transfection brain cells. ADP-LNPs Cre transfected 30% Ai9 mice had no detectable adverse effects on development postnatal growth. addition, neural stem progenitor mRNA, which subsequently proliferated caused over 40% cortical neurons 60% hippocampal be edited treated 10 weeks after birth. Furthermore, using Angelman syndrome, paradigmatic disorder, as disease model, carrying Cas9 gRNA induced indels 21% within 7 days postpartum, underscoring precision approach. These findings LNP/mRNA complexes have transformative tool disorders set stage frontier treating focuses curing genetic diseases before

Язык: Английский

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