Progress in RNA-targeting and Gene Editing Therapies for Transthyretin Amyloidosis Cardiomyopathy
10.12376/j.issn.2097-0501.2023.01.013
- VernacularTitle:RNA靶向和基因编辑药物在转甲状腺素蛋白淀粉样变心肌病中的研究进展
- Author:
Ziran NIU
1
,
2
;
Yang HU
1
,
2
;
Qingyang LIU
1
,
2
;
Yuanyuan MA
1
,
2
;
Jianing LIU
1
,
2
;
Xin LIU
1
,
2
;
Bo ZHANG
1
,
2
Author Information
1. Department of Pharmacy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences &
2. Peking Union Medical College, Beijing 100730, China.
- Publication Type:Journal Article
- Keywords:
ransthyretin amyloidosis caridomyopathy;
siRNA;
antisense oligonucleotide;
gene-editing
- From:
JOURNAL OF RARE DISEASES
2023;2(1):98-104
- CountryChina
- Language:Chinese
-
Abstract:
Transthyretin(TTR) protein is a tetramer protein, synthesized mainly by the liver. TTR can be misfolded and deposited as amyloid fibrilae and deposited in the myocardial interstroma leading to transthyroxin amyloidosis cardiomyopathy (ATTR-CM). ATTR-CM was included in China's First List of Rare Diseases. Therapeutic strategies for ATTR-CM include blocking TTR synthesis in the liver, stabilizing TTR tetramers and destroying TTR fibra. Small molecule drugs such as tafamidis and diflunisal offer new treatment options for patients. Chlorobenzolic acid became the first drug approved by the U.S. Food and Drug Administration for the treatment of ATTR-CM. Small interfering RNA(siRNA)patisiran and antisense oligonucleotide (ASO)inotersen block TTR expression in the liver and have been approved for the treatment of ATTR variant polyneuropathy (ATTRv-PN)and are in phase Ⅲ trials for the treatment of ATTR-CM. Other siRNA drugs, vutrisiran, and ASO, eplontersen, are being evaluated for clinical efficacy. This article reviews the development of RNA-targeted therapeutics and gene-editing drugs using CRISPR-Cas9.
