CRISPR/Cas9 therapeutics: a cure for cancer and other genetic diseases

Abstract

Cancer is caused by a series of alterations in genome and epigenome mostly resulting in activation of oncogenes or inactivation of cancer suppressor genes. Genetic engineering has become pivotal in the treatment of cancer and other genetic diseases, especially the formerly-niche use of clustered regularly interspaced short palindromic repeats (CRISPR) associated with Cas9. In defining its superior use, we have followed the recent advances that have been made in producing CRISPR/Cas9 as a therapy of choice. We also provide important genetic mutations where CRISPRs can be repurposed to create adaptive immunity to fight carcinomas and edit genetic mutations causing it. Meanwhile, challenges to CRISPR technology are also discussed with emphasis on ability of pathogens to evolve against CRISPRs. We follow the recent developments on the function of CRISPRs with different carriers which can efficiently deliver it to target cells; furthermore, analogous technologies are also discussed along CRISPRs, including zinc-finger nuclease (ZFN) and transcription activator-like effector nucleases (TALENs). Moreover, progress in clinical applications of CRISPR therapeutics is reviewed; in effect, patients can have lower morbidity and/or mortality from the therapeutic method with least possible side-effects.

The future is now: cutting edge science and understanding toxicology

“…The CRISPR/Cas9 system has many potential applications for gene editing, such as targeting mutated genes in cancer or genes encoding antibiotic resistance (Khan et al 2016;Muller et al 2016). In CBT, the potential of CRISPR for gene knock-in applications was elegantly discussed by Sakuma and Yamamoto (2017).…”

CRISPR genome editing and its medical applications

“…CRISPR causes a double-stranded cleavage in DNA, which is repaired by the error-prone repair system or homologous recombination. More than 13 different CRISPR systems have been identified so far [20].…”

“…After relative pairing with crRNA, tracrRNA leads to Cas9-CRISPR binding. Then, Cas9 generates a custom cut with its endonuclease property; and after cutting by CRISPR, DNA takes one of the two possible paths: the opposite terminals connecting path, which is prone to error but has better performance, or the homologous recombination path, which is designed based on DNA pattern [20].…”

“…Cancer is generated by oncogenes or tumour suppressor genes for various genetic and epigenetic reasons [2,20]. Therefore, the CRISPR system could potentially treat the disease by generating accurate mutations through turning off the oncogenes or turning on the tumour suppressor genes.…”

Allogeneic transplantation of hematopoietic stem cells: Perspectives and alternatives, own experience

“…В качестве будущей альтернативы алло-ТГСК воз-можно применение системы CRISPR/Cas9 и для ле-чения острых лейкозов с исправлением дефектов аутологичных ГСК. CRISPR/Cas9, как и некоторые другие методики редактирования генома, изучается в лечении различных наследственных заболеваний, ОМЛ, Т-клеточных лимфом, солидных опухолей (мо-дификация Т-клеток с удалением гена мембранного белка PD-1 для противоопухолевой активации Т-лим-фоцитов, что представляется более перспективным, чем применение анти-PD-1-антител), врожденных иммунодефицитов, вируса иммунодефицита челове-ка [140][141][142]. Из более новых технологий изучается белок Cpf1 для системы CRISPR, а также другой спо-соб редактирования генома с использованием белка Natronobacterium gregoryi Argonauteis (NgAgo), кото-рый может обладать потенциально большей точностью и эффективностью по сравнению с СRISPR/Cas9.…”