Maximilian Scheinfeld 

Coronary Artery Disease (CAD) is a disease that involves the buildup of plaque, which eventually causes a heart attack or a stroke. Roughly 10-15% of genetic CAD can be traced to one gene called Antisense Noncoding RNA in the INK4 Locus (ANRIL). ANRIL is an RNA that doesn’t make any proteins. The main function of the gene that codes for it is to regulate gene expression. 

ANRIL comes in long and short isoforms (forms of expression), which are thought to be connected to CAD and cancer growth, respectively. Among these ANRIL isoforms, the ones that are connected to the risk of CAD or cancer are called Risk isoforms, and the ones that are not are called Non-Risk isoforms. 

Two novel methods proposed to knockdown (or suppress expression of) Risk ANRIL are CRISPR/Cas13 and Antisense Oligonucleotides (ASOs). ASOs are a method which involves targeting the mRNA, or instructions for isoforms in order to turn them off, while CRISPR/Cas13 works by going to the isoforms themselves and breaking them down.

Researchers understand that ANRIL is linked to CAD but do not understand exactly how it operates or what we can do to prevent it from causing CAD in people. VSMCs (vascular smooth muscle cells) are important to study because Risk ANRIL in these cells is thought to contribute to the buildup of plaque that causes coronary artery disease.

My project aims to understand the functions of the isoforms and understand if ANRIL can be suppressed in the early stages of the development of VSMCs. We also aim to see if it is possible to save VSMCs that are exhibiting CAD and attempt to revert them to their regular function without CAD. We will use VSMCs and then test if we can knockdown expression or suppress the VSMCs from causing CAD and also if we can save or protect VSMCs in this state and turn them back into normally functioning VSMCs. We will do this by comparing the effectiveness of CRISPR/Cas13 and ASOs.