Goolab Shivani, Scholefield Janine
Bioengineering and Integrated Genomics Group, Future Production Chemicals Cluster, Council for Scientific and Industrial Research, Pretoria, South Africa.
Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Front Genome Ed. 2024 Sep 25;6:1464531. doi: 10.3389/fgeed.2024.1464531. eCollection 2024.
The designer nuclease, CRISPR-Cas9 system has advanced the field of genome engineering owing to its programmability and ease of use. The application of these molecular scissors for genome engineering earned the developing researchers the Nobel prize in Chemistry in the year 2020. At present, the potential of this technology to improve global challenges continues to grow exponentially. CRISPR-Cas9 shows promise in the recent advances made in the Global North such as the FDA-approved gene therapy for the treatment of sickle cell anaemia and β-thalassemia and the gene editing of porcine kidney for xenotransplantation into humans affected by end-stage kidney failure. Limited resources, low government investment with an allocation of 1% of gross domestic production to research and development including a shortage of skilled professionals and lack of knowledge may preclude the use of this revolutionary technology in the Global South where the countries involved have reduced science and technology budgets. Focusing on the practical application of genome engineering, successful genetic manipulation is not easily accomplishable and is influenced by the chromatin landscape of the target locus, guide RNA selection, the experimental design including the profiling of the gene edited cells, which impacts the overall outcome achieved. Our assessment primarily delves into economical approaches of performing efficient genome engineering to support the first-time user restricted by limited resources with the aim of democratizing the use of the technology across low- and middle-income countries. Here we provide a comprehensive overview on existing experimental techniques, the significance for target locus analysis and current pitfalls such as the underrepresentation of global genetic diversity. Several perspectives of genome engineering approaches are outlined, which can be adopted in a resource limited setting to enable a higher success rate of genome editing-based innovations in low- and middle-income countries.
设计核酸酶CRISPR-Cas9系统因其可编程性和易用性推动了基因组工程领域的发展。这些分子剪刀在基因组工程中的应用为相关研究人员赢得了2020年的诺贝尔化学奖。目前，这项技术改善全球挑战的潜力仍在呈指数级增长。CRISPR-Cas9在全球北方地区的最新进展中展现出前景，比如美国食品药品监督管理局批准的用于治疗镰状细胞贫血和β地中海贫血的基因疗法，以及用于终末期肾衰竭患者异种移植的猪肾基因编辑。资源有限、政府研发投入低（仅占国内生产总值的1%），包括缺乏专业技术人员和知识，可能会妨碍这项革命性技术在全球南方国家的使用，这些国家的科技预算已经减少。专注于基因组工程的实际应用，成功的基因操作并非易事，它受到靶位点染色质格局、引导RNA选择、实验设计（包括对基因编辑细胞的分析）的影响，而这些都会影响最终的结果。我们的评估主要深入探讨进行高效基因组工程的经济方法，以支持资源有限的初次使用者，目的是在低收入和中等收入国家普及这项技术的使用。在此，我们全面概述了现有的实验技术、靶位点分析的意义以及当前存在的问题，如全球遗传多样性代表性不足。我们概述了基因组工程方法的几个观点，在资源有限的情况下可以采用这些观点，以提高低收入和中等收入国家基于基因组编辑的创新成功率。
