RNAi technology targeting the FGFR3-TACC3 fusion breakpoint: an opportunity for precision medicine.

ABSTRACT:

Background

Fusion genes form as a result of abnormal chromosomal rearrangements linking previously separate genes into one transcript. The FGFR3-TACC3 fusion gene (F3-T3) has been shown to drive gliomagenesis in glioblastoma (GBM), a cancer that is notoriously resistant to therapy. However, successful targeting of F3-T3 via small molecular inhibitors has not revealed robust therapeutic responses, and specific targeting of F3-T3 has not been achieved heretofore. Here, we demonstrate that depleting F3-T3 using custom siRNA to the fusion breakpoint junction results in successful inhibition of F3-T3+ GBMs, and that exosomes can successfully deliver these siRNAs.

Methods

We engineered 10 unique siRNAs (iF3T3) that specifically spanned the most common F3-T3 breakpoint with varying

SUBMITTER: Parker Kerrigan BC 

PROVIDER: S-EPMC7680176 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature