Publications

Authors:

Nicosia, Lucia; Pranke, Iwona; Latorre, Roberta V.; Murray, Joss B.; Lonetti, Lisa; Cavusoglu-Doran, Kader; Dreano, Elise; Costello, James P.; Carroll, Michael; Melotti, Paola; Sorio, Claudio; Sermet-Gaudelus, Isabelle; Scallan, Martina F.; Harrison, Patrick T.

Title:

Adenine base editing with engineered virus-like particles rescues the CFTR mutation G542X in patient-derived intestinal organoids

Year:

2025

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Format:

Elettronico

Referee:

Sì

Name of journal:

ISCIENCE

ISSN of journal:

2589-0042

N° Volume:

28

Number or Folder:

3

Page numbers:

1-15

Keyword:

cystic fibrosis, base editing, gene therapy, nasal cells, intestinal organoids, CFTR

Short description of contents:

Cystic fibrosis (CF) is a life-shortening autosomal recessive disease, caused by loss-of-function mutations that affect the CF transmembrane conductance regulator (CFTR) anion channel. G542X is the second-most common CF-causing variant, and it does not respond to current CFTR modulator drugs. Our study explores the use of adenine base editing to edit G542X to a non-CF-causing variant, G542R, and recover CFTR function. Using base editor engineered virus-like particles (BE-eVLPs) in patient-derived intestinal organoids, we achieved 2% G542X-to-G542R editing efficiency and restored CFTR-mediated chloride transport to 6.4% of wild-type levels, independent of modulator treatment, and with no bystander edits. This proof-of-principle study demonstrates the potential of base editing to rescue G542X and provides a foundation for future in-vivo applications.

Note:

Cystic fibrosis (CF) is a life-shortening autosomal recessive disease, caused by loss-of-function mutations that affect the CF transmembrane conductance regulator (CFTR) anion channel. G542X is the second- most common CF-causing variant, and it does not respond to current CFTR modulator drugs. Our study ex- plores the use of adenine base editing to edit G542X to a non-CF-causing variant, G542R, and recover CFTR function. Using base editor engineered virus-like particles (BE-eVLPs) in patient-derived intestinal organoids, we achieved 2% G542X-to-G542R editing efficiency and restored CFTR-mediated chloride transport to 6.4% of wild-type levels, independent of modulator treatment, and with no bystander edits. This proof- of-principle study demonstrates the potential of base editing to rescue G542X and provides a foundation for future in-vivo applications.

Product ID:

144628

Handle IRIS:

11562/1157267

Last Modified:

March 14, 2025

Bibliographic citation:

Nicosia, Lucia; Pranke, Iwona; Latorre, Roberta V.; Murray, Joss B.; Lonetti, Lisa; Cavusoglu-Doran, Kader; Dreano, Elise; Costello, James P.; Carroll, Michael; Melotti, Paola; Sorio, Claudio; Sermet-Gaudelus, Isabelle; Scallan, Martina F.; Harrison, Patrick T., Adenine base editing with engineered virus-like particles rescues the CFTR mutation G542X in patient-derived intestinal organoids «ISCIENCE» , vol. 28 , n. 3 , 2025 , pp. 1-15

Consulta la scheda completa presente nel repository istituzionale della Ricerca di Ateneo