CRISPR Based System for Targeted Reduction of Gene Expression


A CRISPR based gene silencing system using sequence specific RNA to repress expression of endogenous transcripts.

Key Benefits

  • Provides a platform to target specific mRNA transcripts in both prokaryotic and eukaryotic cells.
  • Potential therapeutic strategy against pathogenic bacteria and viruses.

Market Summary

RNAi is an indispensable tool to study gene function and is extensively utilized in basic research as well as drug discovery. Due to the ability to specifically target a disease causing protein, RNAi offers the capability to develop personalized treatment. Use of RNAi requires overcoming the hurdle of delivering RNAi systemically and limiting potential side effects. There are no current RNAi drugs on the market, but there are, and have been, clinical trials for ocular and retinal disorders, cancer, kidney disease, and antivirals. Concerns over off target effects, stimulation of immune response, and perturbation to endogenous RNAi machinery have halted previous clinical trials. A method to silence RNA through an alternative pathway may eliminate these pitfalls. In addition, reducing gene expression in prokaryotic organisms has not been explored and leaves an opportunity to develop strategies to suppress infectious pathogens.

Technical Summary

Regulation of gene expression is a critical component of adaptive immunity where the host cell recognizes and destroys aberrant nucleic acid. Eukaryotes employ the RNA interference (RNAi) pathway to target mRNA transcripts specifically for destruction, thwarting protein expression. Bacteria do not have a homologous RNAi system, but contain the newly characterized bacterial clustered regularly interspaced short palindromic repeat (CRISPR) pathway to modulate gene expression. The CRISPR system has been shown previously to target exogenous DNA, but new research from Emory shows that it can specifically target an endogenous transcript to silence expression.

Researchers at Emory identified that the CRISPR pathway modulates specific bacterial transcripts to promote replication in the host cell without stimulating an immune response. The intracellular pathogen, Francisella novicida, uses CRISPR to repress its endogenous transcript, bacterial lipoprotein (BLP). By reducing BLP expression, F. novicida circumvents toll-like receptor 2 activation to prevent initiation of host defenses and pro-inflammatory pathways. Our researchers propose the use of this system to decrease translation of proteins by targeting specific mRNA transcripts in both prokaryotic and eukaryotic cells.

Patent Information

App Type Country Serial No. Patent No. File Date Issued Date Patent Status
EP Registered Country United Kingdom 21175562.4 3919505 1/15/2014 8/30/2023 Issued
Nationalized PCT - United States United States 14/760,113 10,544,405 7/9/2015 1/28/2020 Issued
EP Registered Country France 14740738.1 2946015 7/29/2015 5/26/2021 Issued
EP Registered Country Germany 14740738.1 2946015 7/29/2015 5/26/2021 Issued
EP Registered Country United Kingdom 14740738.1 2946015 7/29/2015 5/26/2021 Issued
Nationalized PCT - Foreign EP 14740738.1 2946015 7/29/2015 5/26/2021 Issued
Nationalized PCT - Foreign China 2014800088805 ZL 2014800088805 8/14/2015 8/31/2021 Issued
Nationalized - Based on Foreign IP Hong Kong 16105130.2 1217728 B 5/5/2016 2/18/2022 Registered
Continuation United States 16/507,745 11,312,945 7/10/2019 4/26/2022 Issued
Divisional EP 21175562.4 3919505 5/24/2021 8/30/2023 Issued
Tech ID: 12224
Published: 12/10/2020