Durable and efficient gene silencing in vivo by hit-and-run epigenome editing
The San Raffaele Telethon Institute for Gene Therapy · Istituti di Ricovero e Cura a Carattere Scientifico · +5 more institutions
Abstract
. However, to unlock its full therapeutic potential, an experimental confirmation of durable epigenetic silencing after the delivery of transient delivery of editors in vivo is needed. To this end, here we targeted Pcsk9, a gene expressed in hepatocytes that is involved in cholesterol homeostasis. In vitro screening of different editor designs indicated that zinc-finger proteins were the best-performing DNA-binding platform for efficient silencing of mouse Pcsk9. A single administration of lipid nanoparticles loaded with the editors' mRNAs almost halved the circulating levels of PCSK9 for nearly one year in mice. Notably, Pcsk9 silencing and accompanying epigenetic repressive marks also persisted after forced…
Citation impact
- FWCI
- 36.08
- Percentile
- 100%
- References
- 59
Authors
7- MAMartino Alfredo Cappelluti
The San Raffaele Telethon Institute for Gene Therapy, Istituti di Ricovero e Cura a Carattere Scientifico, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
- VMValeria Mollica Poeta
The San Raffaele Telethon Institute for Gene Therapy, Istituti di Ricovero e Cura a Carattere Scientifico, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
- SVSara Valsoni
The San Raffaele Telethon Institute for Gene Therapy, Istituti di Ricovero e Cura a Carattere Scientifico, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
- PQPiergiuseppe Quarato
The San Raffaele Telethon Institute for Gene Therapy, Istituti di Ricovero e Cura a Carattere Scientifico, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
- SMSimone Merlin
Università degli Studi del Piemonte Orientale “Amedeo Avogadro”
Topics & keywords
- Gene silencing
- Epigenetics
- Biology
- Epigenome
- DNA methylation
- Cell biology
- Genetics
- Gene