School of Bio Sciences and Technology, VIT University, Vellore, India.
Cellular and Molecular Therapeutics Laboratory, Centre for Biomaterials, Cellular and Molecular Theranostics (CBCMT), VIT University, Vellore, Tamil Nadu, 632014, India.
Heart Fail Rev. 2017 Nov;22(6):795-823. doi: 10.1007/s10741-017-9622-7.
Cardiovascular diseases pose a unique threat to global mortality because it presents as one of the most diverse conglomerations of pathophysiological conditions that can create significant casualty even without straying into its collateral damage. This puts them right beside obesity and cancer in terms of severity. Their pervasive nature and high prevalence prompted biologists to seek newer prophylactic avenues of addressing this global hazard, among which adeno-associated virus (AAV) gene therapy rose to significant prominence. By virtue of its unrivaled clinical safety quotient, AAVs have been used to rectify various subtypes of cardiovascular ailments, beginning from commonly occurring heart failure to vascular diseases. The review focuses on the history of AAV-mediated gene therapy and contemporary breakthroughs in terms of novel innovations in vector engineering to reduce detargeting, immune response, untimely expression, and so on. We have also focused on the molecular world of cardiomyocytes and endothelial cells but interpreted the therapies in a broader context of cardiovascular pathology. The advances made in each mode of intervention as well as the ones that are beyond the scope of AAV gene therapy or has not been approached through AAV gene therapy as of now have been provided in detail to illustrate the bigger picture of where we stand to combat cardiovascular diseases most efficiently.
心血管疾病对全球死亡率构成独特威胁，因为它是病理生理学条件最复杂的组合之一，即使不涉及并发症，也可能造成重大伤亡。就其严重程度而言，它可与肥胖症和癌症相提并论。鉴于其普遍存在和高发病率，生物学家寻求更新的预防措施来应对这一全球危害，其中腺相关病毒 (AAV) 基因治疗引起了广泛关注。由于其无与伦比的临床安全性，AAV 已被用于纠正各种心血管疾病，从常见的心力衰竭到血管疾病。本综述重点介绍了 AAV 介导的基因治疗的历史，以及在载体工程方面的新型创新方面的最新突破，以减少非靶向性、免疫反应、表达时机不当等问题。我们还关注了心肌细胞和内皮细胞的分子世界，但在更广泛的心血管病理学背景下解释了这些疗法。详细介绍了每种干预模式的进展，以及那些超出 AAV 基因治疗范围或尚未通过 AAV 基因治疗解决的进展，以说明我们在有效对抗心血管疾病方面所处的位置。
