Gene therapy for cancer by mutant HSV deleted apoptosis-inhibited gene

A mutant HSV (mtHSV) deleted icp34.5, an apoptosis-inhibiting gene was constructed. It is supposed that the mtHSV can replicate in p53-deficient cells selectively and lead to oncolysis targetedly. Mice tumor model harboring sarcoma cell line s-180 was developed and the mtHSV was injected into the tumors. We found that the mean volume and weight of tumors of early therapeutic group(ETG) were reduced 49.29% and 38.31% of that of control tumors. In the mid-term group (MTG), the redutcion rate were 26.9% and 24.52% respectively. Foundation item: Supported by Foundation of 863 New Hi-technique Research (39880031); Research Fund for the Doctoral Programm of Higher Education (RFDP98048615); Chen-guang Project of Wuhan City (20005004024). Biography: Lan Ping (1971-), female, Ph.D candidate, research direction: molecular virology.     

Gene therapy: X-SCID transgene leukaemogenicity

Gene therapy has been remarkably effective for the immunological reconstitution of patients with severe combined immune deficiency, but the occurrence of leukaemia in a few patients has stimulated debate about the safety of the procedure and the mechanisms of leukaemogenesis. Woods et al. forced high expression of the corrective therapeutic gene IL2RG, which encodes the gamma-chain of the interleukin-2 receptor, in a mouse model of the disease and found that tumours appeared in a proportion of cases. Here we show that transgenic IL2RG does not necessarily have potent intrinsic oncogenic properties, and argue that the interpretation of this observation with respect to human trials is overstated.     

Gene therapy in perspective

Weatherall assesses prospects for the development of clinically useful gene therapy. He considers progress to date, technical difficulties, and ethical concerns.     

单基因遗传疾病的基因疗法

基因疗法是全球突破性技术之一,在单基因遗传疾病治疗中已取得突破性进展。阐述了不同的基因疗法策略、载体和基因编辑技术的特点,综述了脊髓性肌萎缩症、Leber先天性黑蒙2型、血友病、β-地中海贫血的发病机理、临床表现、基因疗法的开发进程以及临床试验情况。目前,上述4种单基因疾病的9种基因疗法已分别取得美国食品药品监督管理局突破性疗法资格、欧洲药品管理局的优先药物资格或者已经批准上市。基因疗法的研究还面临着许多挑战,但随着科学研究的深入和科学技术的不断发展,将有更多的患者获得治疗。     

心血管疾病的基因治疗

基因治疗在先天遗传性以及后天获得性心血管疾病治疗中均具有广阔的发展前景. 对心血管疾病致病机理的深入认识和疾病基因组学研究的发展, 进一步促进了临床前基因治疗的研究进展. 但基因治疗过程中存在的机体细胞免疫反应、外源基因表达水平不足、在体基因转导效率低下等因素都成为基因治疗临床应用转化的瓶颈. 近年来, 基因导入载体和基因组编辑技术的发展为上述问题的改善和解决提供了新的思路. 目前成族规律间隔短回文重复序列(clustered regularly interspaced short palindromic repeats, CRISPR)/Cas9 基因组编辑技术已经成功应用于动物模型的在体基因编辑, 达到了显著改善血脂指标的疗效. 进一步研究体内组织特异和高效的基因导入方式, 提高基因编辑的靶向效率和特异性, 并建立全面有效的安全评估实验体系, 将推动基因治疗向临床应用的转化. 针对心血管疾病基因治疗中基因导入载体的研究以及CRISPR/Cas9 基因组编辑技术的应用展开讨论.     

Myocardial gene therapy.

Gene therapy is proving likely to be a viable alternative to conventional therapies in coronary artery disease and heart failure. Phase 1 clinical trials indicate high levels of safety and clinical benefits with gene therapy using angiogenic growth factors in myocardial ischaemia. Although gene therapy for heart failure is still at the pre-clinical stage, experimental data indicate that therapeutic angiogenesis using short-term gene expression may elicit functional improvement in affected individuals.     

基因治疗及其研究进展

基因治疗作为一种新型的疾病治疗手段 ,正在广泛用于血友病、糖尿病、癌症、心血管病、爱滋病等多种疾病的治疗领域 .基因治疗的一般步骤包括 :目的基因的转移和目的基因的表达两个方面 .其中目的基因的导入和目的基因表达的精确调控是两个关键步骤 .新发展的还有反义疗法以及应用核酶进行基因治疗等 .本文就基因治疗的基本步骤、基因治疗的对象、方式及基因治疗的现状和前景作一个简单介绍