Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA.
Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, USA.
Signal Transduct Target Ther. 2021 Feb 8;6(1):53. doi: 10.1038/s41392-021-00487-6.
Throughout its 40-year history, the field of gene therapy has been marked by many transitions. It has seen great strides in combating human disease, has given hope to patients and families with limited treatment options, but has also been subject to many setbacks. Treatment of patients with this class of investigational drugs has resulted in severe adverse effects and, even in rare cases, death. At the heart of this dichotomous field are the viral-based vectors, the delivery vehicles that have allowed researchers and clinicians to develop powerful drug platforms, and have radically changed the face of medicine. Within the past 5 years, the gene therapy field has seen a wave of drugs based on viral vectors that have gained regulatory approval that come in a variety of designs and purposes. These modalities range from vector-based cancer therapies, to treating monogenic diseases with life-altering outcomes. At present, the three key vector strategies are based on adenoviruses, adeno-associated viruses, and lentiviruses. They have led the way in preclinical and clinical successes in the past two decades. However, despite these successes, many challenges still limit these approaches from attaining their full potential. To review the viral vector-based gene therapy landscape, we focus on these three highly regarded vector platforms and describe mechanisms of action and their roles in treating human disease.
纵观基因治疗 40 年的发展历程，其经历了许多转变。该领域在对抗人类疾病方面取得了重大进展，为治疗选择有限的患者和家庭带来了希望，但也遭遇了许多挫折。使用此类在研药物治疗患者导致了严重的不良反应，甚至在极少数情况下导致死亡。这一分水岭领域的核心是基于病毒的载体，这些载体是研究人员和临床医生开发强大药物平台的输送工具，彻底改变了医学的面貌。在过去 5 年中，基因治疗领域出现了一波基于病毒载体的药物，这些药物已获得监管部门的批准，具有多种设计和用途。这些方法包括基于载体的癌症疗法，以及治疗具有改变生活的结果的单基因疾病。目前，三种关键的载体策略基于腺病毒、腺相关病毒和慢病毒。在过去二十年中，它们在临床前和临床成功方面处于领先地位。然而，尽管取得了这些成功，但许多挑战仍然限制了这些方法充分发挥其潜力。为了回顾基于病毒载体的基因治疗领域，我们重点关注这三种备受关注的载体平台，并描述它们的作用机制及其在治疗人类疾病中的作用。
