Endogenous spacing enables co-processing of microRNAs and efficient combinatorial RNAi. Academic Article uri icon

Overview

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.

publication date

  • June 21, 2022

Identity

PubMed Central ID

  • PMC9308131

Scopus Document Identifier

  • 80051513341

Digital Object Identifier (DOI)

  • 10.1101/gad.17269211

PubMed ID

  • 35880017

Additional Document Info

volume

  • 2

issue

  • 7