An investigational RNAi therapeutic targeting Factor XII (ALN-F12) for the treatment of hereditary angioedema.
Angioedemas, Hereditary
/ drug therapy
Animals
Bradykinin
/ biosynthesis
Capillary Permeability
/ drug effects
Complement C1 Inhibitor Protein
/ genetics
Factor XII
/ analysis
Female
Humans
Kininogens
/ metabolism
Macaca fascicularis
Mice
Mice, Inbred C57BL
RNA Interference
RNA, Small Interfering
/ genetics
Rats
Factor XII
GalNAc-siRNA
HK cleavage
bradykinin
hereditary angioedema
vascular permeability
Journal
RNA (New York, N.Y.)
ISSN: 1469-9001
Titre abrégé: RNA
Pays: United States
ID NLM: 9509184
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
20
09
2018
accepted:
20
11
2018
pubmed:
23
11
2018
medline:
21
3
2019
entrez:
23
11
2018
Statut:
ppublish
Résumé
Hereditary angioedema (HAE) is a genetic disorder mostly caused by mutations in the C1 esterase inhibitor gene (C1INH) that results in poor control of contact pathway activation and excess bradykinin generation. Bradykinin increases vascular permeability and is ultimately responsible for the episodes of swelling characteristic of HAE. We hypothesized that the use of RNA interference (RNAi) to reduce plasma Factor XII (FXII), which initiates the contact pathway signaling cascade, would reduce contact pathway activation and prevent excessive bradykinin generation. A subcutaneously administered GalNAc-conjugated small-interfering RNA (siRNA) targeting
Identifiants
pubmed: 30463937
pii: rna.068916.118
doi: 10.1261/rna.068916.118
pmc: PMC6348991
doi:
Substances chimiques
Complement C1 Inhibitor Protein
0
Kininogens
0
RNA, Small Interfering
0
SERPING1 protein, human
0
Factor XII
9001-30-3
Bradykinin
S8TIM42R2W
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
255-263Informations de copyright
© 2019 Liu et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.
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