A CRISPR activator array has been developed that targets promoters of long non-coding RNAs and in turn induces the upregulation of microRNAs, a valuable approach for regulating gene mechanisms, developing novel therapeutic strategies, and advancing precision medicine.
Application
Development Status
IP Status
Commercial Offering
Opportunity
The technology has been utilised in the context of pathological vascular remodelling following injury to the vasculature, a major unmet clinical need. Vascular smooth muscle cells (vSMCs) have a crucial role in pathological vascular remodelling, and targeting vSMCs may hold significant promise for treating cardiovascular diseases.
A key factor regulating cellular states, e.g., vSMC identity, is the synergistic expression levels of noncoding RNAs, long noncoding RNAs (lncRNAs) and microRNAs (miRNAs). Complex noncoding genomic loci can have multiple promoters and include different classes of noncoding RNA molecules.
There are several strategies to enhance RNA expression of genomic loci, however (1) the transcript size might exceed the vector limit; (2) the locus could include multiple transcripts which cannot be simultaneously co-expressed; (3) the exact structure of the locus might not be well annotated.
Technology Overview
Elevating the expression of a large lncRNA axis, as opposed to overexpressing its individual components, presents a preventive effect on the development of vein graft failure. This is done by utilising CRISPR activator technology to activate the promoter region of noncoding RNA axes, CARMN and MIR503HG. Both lncRNAs have been shown to be downregulated in different pathological contexts involving primary vascular cells, therefore the activation of their expression is important to maintain cell identity.
Our results show that it is possible to activate the expression of the lncRNA transcripts concomitantly to microRNAs by activating the main promoter of the noncoding RNA axes. We also have shown that it is possible to use this strategy in primary smooth muscle cells opening the possibility for translation to a clinical setting.
Benefits
Quote: TEC1104437
Technology Transfer Manager
Edinburgh Innovations
The University of Edinburgh