Endogenous spacing enables co-processing of microRNAs and efficient combinatorial RNAi.
Cell Rep Methods
; 2(7): 100239, 2022 07 18.
Article
en En
| MEDLINE
| ID: mdl-35880017
ABSTRACT
We present Multi-miR, a microRNA-embedded shRNA system modeled after endogenous microRNA clusters that enables simultaneous expression of up to three or four short hairpin RNAs (shRNAs) from a single promoter without loss of activity, enabling robust combinatorial RNA interference (RNAi). We further developed complementary all-in-one vectors that are over one log-scale more sensitive to doxycycline-mediated activation in vitro than previous methods and resistant to shRNA inactivation in vivo. We demonstrate the utility of this system for intracranial expression of shRNAs in a glioblastoma model. Additionally, we leverage this platform to target the redundant RAF signaling node in a mouse model of KRAS-mutant cancer and show that robust combinatorial synthetic lethality efficiently abolishes tumor growth.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
MicroARNs
Límite:
Animals
Idioma:
En
Revista:
Cell Rep Methods
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos