Approaches to Therapeutic Gene Editing in Alpha-1 Antitrypsin Deficiency

Alisha M Gruntman; Wen Xue; Terence R Flotte

doi:10.1007/978-1-0716-3605-3_2

Approaches to Therapeutic Gene Editing in Alpha-1 Antitrypsin Deficiency

Methods Mol Biol. 2024:2750:11-17. doi: 10.1007/978-1-0716-3605-3_2.

Authors

Alisha M Gruntman¹, Wen Xue¹, Terence R Flotte²

Affiliations

¹ Department of Pediatrics, University of Massachusetts Chan Medical School, Worcester, MA, USA.
² Department of Pediatrics, University of Massachusetts Chan Medical School, Worcester, MA, USA. terry.flotte@umassmed.edu.

PMID: 38108963
DOI: 10.1007/978-1-0716-3605-3_2

Abstract

Five distinct gene therapy approaches have been developed for treating AATD. These approaches include knockout of the mutant (PiZ) allele by introduction of double-strand breaks (DSBs) and subsequent creation of insertions and deletions (indels) by DSB repair, homology-directed repair (HDR) targeted to the mutation site, base editing, prime editing, and alternatively targeted knock-in techniques. Each approach will be discussed and a brief summary of a standard CRISPR-Cas9 targeting method will be presented.

Keywords: Base editing; Double-strand breaks; Homology-directed repair; Indels; Prime editing.

MeSH terms

Alleles
Gene Editing*
Genetic Therapy
Humans
INDEL Mutation
Mutation
alpha 1-Antitrypsin Deficiency* / genetics
alpha 1-Antitrypsin Deficiency* / therapy