PMID- 36825473
OWN - NLM
STAT- MEDLINE
DCOM- 20230314
LR  - 20230326
IS  - 1744-7682 (Electronic)
IS  - 1471-2598 (Linking)
VI  - 23
IP  - 3
DP  - 2023 Mar
TI  - Gene therapy for alpha-1 antitrypsin deficiency: an update.
PG  - 283-291
LID - 10.1080/14712598.2023.2183771 [doi]
AB  - INTRODUCTION: Altering the human genetic code has been explored since the early 
      1990s as a definitive answer for the treatment of monogenic and acquired diseases 
      which do not respond to conventional therapies. In Alpha-1 antitrypsin deficiency 
      (AATD) the proper synthesis and secretion of alpha-1 antitrypsin (AAT) protein is 
      impaired, leading to its toxic hepatic accumulation along with its pulmonary 
      insufficiency, which is associated with parenchymal proteolytic destruction. 
      Because AATD is caused by mutations in a single gene whose correction alone would 
      normalize the mutant phenotype, it has become a popular target for both 
      augmentation gene therapy and gene editing. Although gene therapy products are 
      already a reality for the treatment of some pathologies, such as inherited 
      retinal dystrophy and spinal muscular atrophy, AATD-related pulmonary and, 
      especially, liver diseases still lack effective therapeutic options. AREAS 
      COVERED: Here, we review the course, challenges, and achievements of AATD gene 
      therapy as well as update on new strategies being developed. EXPERT OPINION: 
      Reaching safe and clinically effective expression of the AAT is currently the 
      greatest challenge for AATD gene therapy. The improvement and emergence of 
      technologies that use gene introduction, silencing and correction hold promise 
      for the treatment of AATD.
FAU - Pires Ferreira, Debora
AU  - Pires Ferreira D
AD  - Department of Pediatrics, University of Massachusetts Chan Medical School, 
      Worcester, MA, United States.
FAU - Gruntman, Alisha M
AU  - Gruntman AM
AD  - Department of Pediatrics, University of Massachusetts Chan Medical School, 
      Worcester, MA, United States.
FAU - Flotte, Terence R
AU  - Flotte TR
AD  - Department of Pediatrics, University of Massachusetts Chan Medical School, 
      Worcester, MA, United States.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20230302
PL  - England
TA  - Expert Opin Biol Ther
JT  - Expert opinion on biological therapy
JID - 101125414
RN  - 0 (alpha 1-Antitrypsin)
SB  - IM
MH  - Humans
MH  - *alpha 1-Antitrypsin Deficiency/genetics/pathology/therapy
MH  - alpha 1-Antitrypsin/genetics/metabolism/therapeutic use
MH  - Lung/pathology
MH  - Gene Editing
MH  - Genetic Therapy
OTO - NOTNLM
OT  - AAV vectors
OT  - Alpha-1 antitrypsin deficiency
OT  - CRISPR-Cas9
OT  - editing guide RNA gene therapy
EDAT- 2023/02/25 06:00
MHDA- 2023/03/15 06:00
CRDT- 2023/02/24 04:35
PHST- 2023/02/25 06:00 [pubmed]
PHST- 2023/03/15 06:00 [medline]
PHST- 2023/02/24 04:35 [entrez]
AID - 10.1080/14712598.2023.2183771 [doi]
PST - ppublish
SO  - Expert Opin Biol Ther. 2023 Mar;23(3):283-291. doi: 
      10.1080/14712598.2023.2183771. Epub 2023 Mar 2.