Multiplex Genome Modifications of Astrocytes Through CRISPR Dead Cas9: A Novel Candidate Therapy for Chronic Ischemic Stroke

Abstract

A stroke is an enervating injury to the brain that occurs from a stoppage in blood supply (ischemic stroke) or bleeding (hemorrhagic) in a hemisphere of the brain. Globally, about 10 million deaths per year are recorded because of stroke. There has been no definitive FDA-approved treatment for chronic ischemic stroke without any side effects so far. Therefore, the search for new therapies is necessary. In this paper, after investigating several studies online, on Google Scholar, PubMed, and Scopus, we hypothesized improving the complications of chronic ischemic stroke in induced Sprague-Dawley rat model by intraluminal suture middle cerebral artery occlusion (MCAo), utilizing the combination of cell therapy and gene therapy. A new version of astrocytes is proposed by making some changes in their genome. To gain this goal, a gene profile including IL-38 (the most modern anti-inflammatory agent, which barricades inflammatory re- sponse factors), BRAG-1 (an anti-apoptotic gene from BCL-2 family), IL-38 and BRAG-1’s complementary scaffold RNAs for their expression by deadCas9 (dCas9), complementary scaffold RNAs of LZK and MST-1 for their deletion, and deadCas9 gene is used. Based on studies and documents, we hypothesized using modified astrocytes by dCas9, which is the most accurate genome-editing technology