Novelty in improvement of CAR T cell-based immunotherapy with the aid of CRISPR system

Abstract Introduction Chimeric Antigen Receptor (CAR) T cells have tremendous potentials for cancer treatment; however, various challenges impede their universal use. These restrictions include the poor function of T cells in tumor microenvironments, the shortage of tumor-specific antigens and, finally, the high cost and time-consuming process, as well as the poor scalability of the method. Creative gene-editing tools have addressed each of these limitations and introduced next generation products for cell therapy. The clustered regularly interspaced short palindromic repeats-associated endonuclease 9 (CRISPR/Cas9) system has triggered a revolution in biology fields, as it has a great capacity for genetic manipulation. Method In this review, we considered the latest development of CRISPR/Cas9 methods for the chimeric antigen receptor T cell (CAR T)-based immunotherapy. Results The ability of the CRISPR/Cas9 system to generate the universal CAR T cells and also potent T cells that are persistent against exhaustion and inhibition was explored. Conclusion: We explained CRISPR delivery methods, as well as addressing safety concerns related to the use of the CRISPR/Cas9 system and their potential solutions.

Membrane-active metabolites produced by soil actinomycetes using chromatic phospholipid/polydiacetylene vesicles.

Increased resistance of pathogens toward existing antibiotics has compelled the research efforts to introduce new antimicrobial substances. Drugs with new and less resistant-prone targets to antimicrobial activity have a high priority for drug development activities. Cell membrane seems to be a potential target for new antibiotic agent development to overcome resistance. In this study, A total number of 67 actinomycetes were isolated from the soil samples collected from desert, farming and mineral parts of Iran. We used a chromatic sensor as a membrane model that was set up for the target of antimicrobial metabolites of actinomycetes isolated from the soil. The sensors particles were composed of phospholipid and polymerized polydiacetylene (PDA) lipids. These polymers exhibited color change following interaction with membrane-active metabolites. The color change was due to structural disorder in the lipids following their interaction with membrane-active metabolites. The resultant color change was recorded by fluorescent microscope and easily recognizable by naked eye as well. Sixteen strains were isolated which produced antimicrobial metabolites and were effective against test microorganisms (Escherichia coli, Candida albicans and Saccharomyces cerevisiae ). A total number of 3 out of 16 strains produced membrane-active metabolites. These 3 strains were identified using 16s rRNA as Streptomyces sp and submitted to GenBank (accession no. JN180853; JN180854; JN180855).