Goldspiel B R, Green L, Calis K A
Pharmacy Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892.
Clin Pharm. 1993 Jul;12(7):488-505.
Current concepts in gene transfer and its application to the treatment of human genetic disorders, cancer, and other diseases are discussed. Gene therapy is a technique in which a functioning gene is inserted into a human cell to correct a genetic error or to introduce a new function to the cell. Many methods, including retroviral vectors, have been developed for ex vivo and in vivo gene insertion into cells. Some pharmacists have likened gene therapy to a sophisticated form of drug delivery and have envisioned an active role for the pharmacy profession. There are several safety and ethical issues related to manipulating the human genome that need to be understood. Current gene therapy efforts focus on gene insertion into somatic (nongerminal) cells only. Gene therapy has the potential to revolutionize the treatment of genetic disorders, diseases associated with a genetic component (e.g., cystic fibrosis), cancer, AIDS, and many other diseases. Gene transfer may also be used to better understand the biology of disease processes, such as the source of relapse in bone marrow transplant patients. The human genome project will undoubtedly lead to the identification, characterization, and understanding of genes that are responsible for many human diseases, and gene therapy trials are sure to expand accordingly. To date, over 40 clinical trials have been approved and more than 110 patients have been entered in gene therapy studies. There are still many technical obstacles to overcome before gene therapy can have widespread application. Injectable vectors need to be developed to simplify foreign gene administration. Perhaps the biggest problem to overcome will be engineering the target cells to be able to regulate gene expression according to physiologic needs. Pharmacists should become knowledgeable about gene transfer techniques and possible clinical applications of gene therapy to keep abreast of the newest trends in medicine.
本文讨论了基因转移的当前概念及其在人类遗传疾病、癌症和其他疾病治疗中的应用。基因治疗是一种将功能正常的基因插入人体细胞以纠正基因错误或为细胞引入新功能的技术。已经开发了许多方法，包括逆转录病毒载体，用于体外和体内将基因插入细胞。一些药剂师将基因治疗比作一种复杂的药物递送形式，并设想了药学专业的积极作用。与操纵人类基因组相关的几个安全和伦理问题需要了解。目前的基因治疗努力仅专注于将基因插入体细胞（非生殖细胞）。基因治疗有可能彻底改变遗传疾病、与遗传成分相关的疾病（如囊性纤维化）、癌症、艾滋病和许多其他疾病的治疗。基因转移还可用于更好地理解疾病过程的生物学，例如骨髓移植患者复发的原因。人类基因组计划无疑将导致对许多人类疾病相关基因的鉴定、表征和理解，基因治疗试验也必将相应扩大。迄今为止，已有40多项临床试验获得批准，超过110名患者进入基因治疗研究。在基因治疗能够广泛应用之前，仍有许多技术障碍需要克服。需要开发可注射载体以简化外源基因的给药。也许要克服的最大问题将是对靶细胞进行工程改造，使其能够根据生理需要调节基因表达。药剂师应该了解基因转移技术和基因治疗可能的临床应用，以跟上医学的最新趋势。
