摘要
自基因治疗的初期起,在酶缺乏和肌肉疾病的修正治疗方面肌肉一直是研究最多的靶组织之一。现已进行了一些腺相关病毒(AAV)载体的临床前和临床研究,并已在基因转移技术上取得了可喜的进展,从对血清型新型AVV的识别到新型载体转移技术的发展。同时,在宿主免疫系统及其与载体和转入基因在肌肉水平上的相互作用等方面也取得了重大突破。特别是,潜在肌肉炎症的作用,影响肌肉的几种疾病的特点,已在对AVV载体基因转移的潜在不利影响方面得到确认。同时,骨骼肌涉及的驻留的调节T细胞特有的反馈免疫调节机制已被确定,至少在某种程度上,对维持肌肉炎症和再生过程中肌肉内稳态发挥着重要作用。设计一些策略来打破机体(免疫系统)的无反应性平衡,以改善通过AAV载体进行肌肉基因转移的安全性和有效性。
关键词: AVV载体(腺相关病毒载体),肌肉,临床试验,免疫反应,耐受性
Current Gene Therapy
Title:The Skeletal Muscle Environment and Its Role in Immunity and Tolerance to AAV Vector-Mediated Gene Transfer
Volume: 15 Issue: 4
Author(s): Florence Boisgerault and Federico Mingozzi
Affiliation:
关键词: AVV载体(腺相关病毒载体),肌肉,临床试验,免疫反应,耐受性
摘要: Since the early days of gene therapy, muscle has been one the most studied tissue targets for the correction of enzyme deficiencies and myopathies. Several preclinical and clinical studies have been conducted using adeno-associated virus (AAV) vectors. Exciting progress has been made in the gene delivery technologies, from the identification of novel AAV serotypes to the development of novel vector delivery techniques. In parallel, significant knowledge has been generated on the host immune system and its interaction with both the vector and the transgene at the muscle level. In particular, the role of underlying muscle inflammation, characteristic of several diseases affecting the muscle, has been defined in terms of its potential detrimental impact on gene transfer with AAV vectors. At the same time, feedback immunomodulatory mechanisms peculiar of skeletal muscle involving resident regulatory T cells have been identified, which seem to play an important role in maintaining, at least to some extent, muscle homeostasis during inflammation and regenerative processes. Devising strategies to tip this balance towards unresponsiveness may represent an avenue to improve the safety and efficacy of muscle gene transfer with AAV vectors.
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Florence Boisgerault and Federico Mingozzi , The Skeletal Muscle Environment and Its Role in Immunity and Tolerance to AAV Vector-Mediated Gene Transfer, Current Gene Therapy 2015; 15 (4) . https://dx.doi.org/10.2174/1566523215666150630121750
DOI https://dx.doi.org/10.2174/1566523215666150630121750 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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