Ashmore-Harris Candice, Fruhwirth Gilbert O
Imaging Therapy and Cancer Group, Dept of Imaging Chemistry & Biology, School of Biomedical Engineering & Imaging Sciences, St Thomas' Hospital, King's College London (KCL), London, SE1 7EH, UK.
Centre for Stem Cells & Regenerative Medicine, School of Basic and Medical Biosciences, Guy's Hospital, KCL, London, SE1 9RT, UK.
Clin Transl Med. 2020 Feb 7;9(1):15. doi: 10.1186/s40169-020-0268-z.
The clinical application of ex vivo gene edited cell therapies first began a decade ago with zinc finger nuclease editing of autologous CD4 T-cells. Editing aimed to disrupt expression of the human immunodeficiency virus co-receptor gene CCR5, with the goal of yielding cells resistant to viral entry, prior to re-infusion into the patient. Since then the field has substantially evolved with the arrival of the new editing technologies transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR), and the potential benefits of gene editing in the arenas of immuno-oncology and blood disorders were quickly recognised. As the breadth of cell therapies available clinically continues to rise there is growing interest in allogeneic and off-the-shelf approaches and multiplex editing strategies are increasingly employed. We review here the latest clinical trials utilising these editing technologies and consider the applications on the horizon.
离体基因编辑细胞疗法的临床应用始于十年前，当时对自体CD4 T细胞进行了锌指核酸酶编辑。编辑的目的是破坏人类免疫缺陷病毒共受体基因CCR5的表达，目标是在重新注入患者体内之前产生对病毒进入具有抗性的细胞。从那时起，随着新的编辑技术——转录激活样效应核酸酶（TALENs）和成簇规律间隔短回文重复序列（CRISPR）的出现，该领域有了实质性的发展，并且基因编辑在免疫肿瘤学和血液疾病领域的潜在益处很快得到认可。随着临床上可用的细胞疗法的广度不断增加，人们对同种异体和现成方法的兴趣日益浓厚，并且越来越多地采用多重编辑策略。我们在此回顾利用这些编辑技术的最新临床试验，并考虑未来的应用。
