Innovative Strategies of Reprogramming Immune System Cells by Targeting CRISPR/Cas9-Based Genome-Editing Tools: A New Era of Cancer Management

Khaled S Allemailem,1 Mohammed A Alsahli,1 Ahmad Almatroudi,1 Faris Alrumaihi,1 Waleed Al Abdulmonem,2 Amira A Moawad,3 Wanian M Alwanian,1 Nahlah Makki Almansour,4 Arshad Husain Rahmani,1 Amjad Ali Khan5 1Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia; 2Department of Pathology, College of Medicine, Qassim University, Buraydah, Saudi Arabia; 3Friedrich-Loeffler-Institut, Institute of Bacterial Infections and Zoonoses, Jena, Germany; 4Department of Biology, College of Science, University of Hafr Al Batin, Hafr Al Batin, Saudi Arabia; 5Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi ArabiaCorrespondence: Amjad Ali Khan, Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah, 51452, Saudi Arabia, Tel +966-16-3800050 Ext. 15445, Fax +966-16-3801628, Email [email protected]: The recent developments in the study of clustered regularly interspaced short palindromic repeats/associated protein 9 (CRISPR/Cas9) system have revolutionized the art of genome-editing and its applications for cellular differentiation and immune response behavior. This technology has further helped in understanding the mysteries of cancer progression and possible designing of novel antitumor immunotherapies. CRISPR/Cas9-based genome-editing is now often used to engineer universal T-cells, equipped with recombinant T-cell receptor (TCR) or chimeric antigen receptor (CAR). In addition, this technology is used in cytokine stimulation, antibody designing, natural killer (NK) cell transfer, and to overcome immune checkpoints. The innovative potential of CRISPR/Cas9 in preparing the building blocks of adoptive cell transfer (ACT) immunotherapy has opened a new window of antitumor immunotherapy and some of them have gained FDA approval. The manipulation of immunogenetic regulators has opened a new interface for designing, implementation and interpretation of CRISPR/Cas9-based screening in immuno-oncology. Several cancers like lymphoma, melanoma, lung, and liver malignancies have been treated with this strategy, once thought to be impossible. The safe and efficient delivery of CRISPR/Cas9 system within the immune cells for the genome-editing strategy is a challenging task which needs to be sorted out for efficient immunotherapy. Several targeting approaches like virus-mediated, electroporation, microinjection and nanoformulation-based methods have been used, but each procedure offers some limitations. Here, we elaborate the recent updates of cancer management through immunotherapy in partnership with CRISPR/Cas9 technology. Further, some innovative methods of targeting this genome-editing system within the immune system cells for reprogramming them, as a novel strategy of anticancer immunotherapy is elaborated. In addition, future prospects and clinical trials are also discussed.Keywords: CRISPR/Cas9, tumor microenvironment, immune response, molecular targeted therapy, cancer immunotherapy, nanotechnology, clinical stud

Emerging evidence for functional peptides encoded by short open reading frames

Short open reading frames (sORFs) are a common feature of all genomes, but their coding potential has mostly been disregarded, partly because of the difficulty in determining whether these sequences are translated. Recent innovations in computing, proteomics and high-throughput analyses of translation start sites have begun to address this challenge and have identified hundreds of putative coding sORFs. The translation of some of these has been confirmed, although the contribution of their peptide products to cellular functions remains largely unknown. This Review examines this hitherto overlooked component of the proteome and considers potential roles for sORF-encoded peptides