Recent Advances in Therapeutics and Manufacturing Processes of Recombinant Adeno-Associated Virus for the Treatment of Lung Diseases.

IF 3.8 4区 医学 Q2 GENETICS & HEREDITY
Luis Sorroza-Martinez, Mia Pelletier, David Guay, Bruno Gaillet
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引用次数: 0

Abstract

Developing delivery vectors capable of transducing genetic material across the lung epithelia and mucus barrier is a major challenge and of great interest to enable gene therapies to treat pulmonary diseases. Recombinant Adeno-associated Viruses (rAAVs) have emerged as attractive candidates among viral and non-viral vectors due to their broad tissue tropism, ability to transduce dividing and quiescent cells, and their safety profile in current human applications. While rAAVs have demonstrated safety in earlier clinical trials for lung disease applications, there are still some limitations regarding rAAV-transgene delivery in pulmonary cells. Thus, further improvements in rAAV engineering are needed to enhance the effectiveness of rAAV-based therapies for lung diseases. Such therapies could benefit patients with chronic lung diseases, such as asthma, chronic obstructive pulmonary disease, pulmonary hypertension, and cystic fibrosis, among others, by regulating hereditary gene mutations or acquired gene deregulations causing these conditions. Alongside therapeutic development, advances in the rAAV production process are essential to meet increasing production demands, while reducing manufacturing costs. This review discusses current challenges and recent advances in the field of rAAV engineering and manufacturing to encourage the clinical development of new pulmonary gene therapy treatments.

用于治疗肺部疾病的重组腺相关病毒疗法和制造工艺的最新进展。
开发能够跨越肺上皮细胞和粘液屏障转导遗传物质的递送载体是一项重大挑战,也是治疗肺部疾病的基因疗法的重要兴趣所在。重组腺相关病毒(rAAV)因其广泛的组织滋养性、转导分裂细胞和静止细胞的能力以及在目前人类应用中的安全性,已成为病毒和非病毒载体中极具吸引力的候选者。虽然 rAAV 在早期肺部疾病应用的临床试验中已证明其安全性,但在肺细胞中转导 rAAV 基因方面仍存在一些局限性。因此,需要进一步改进 rAAV 工程,以提高基于 rAAV 的肺病疗法的有效性。这种疗法可以通过调节导致哮喘、慢性阻塞性肺病、肺动脉高压和囊性纤维化等疾病的遗传性基因突变或获得性基因失调,使慢性肺病患者受益。在开发疗法的同时,rAAV 生产工艺的进步对于满足日益增长的生产需求并降低生产成本至关重要。本综述将讨论 rAAV 工程和生产领域当前面临的挑战和最新进展,以促进新型肺基因疗法的临床开发。
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来源期刊
Current gene therapy
Current gene therapy 医学-遗传学
CiteScore
6.70
自引率
2.80%
发文量
46
期刊介绍: Current Gene Therapy is a bi-monthly peer-reviewed journal aimed at academic and industrial scientists with an interest in major topics concerning basic research and clinical applications of gene and cell therapy of diseases. Cell therapy manuscripts can also include application in diseases when cells have been genetically modified. Current Gene Therapy publishes full-length/mini reviews and original research on the latest developments in gene transfer and gene expression analysis, vector development, cellular genetic engineering, animal models and human clinical applications of gene and cell therapy for the treatment of diseases. Current Gene Therapy publishes reviews and original research containing experimental data on gene and cell therapy. The journal also includes manuscripts on technological advances, ethical and regulatory considerations of gene and cell therapy. Reviews should provide the reader with a comprehensive assessment of any area of experimental biology applied to molecular medicine that is not only of significance within a particular field of gene therapy and cell therapy but also of interest to investigators in other fields. Authors are encouraged to provide their own assessment and vision for future advances. Reviews are also welcome on late breaking discoveries on which substantial literature has not yet been amassed. Such reviews provide a forum for sharply focused topics of recent experimental investigations in gene therapy primarily to make these results accessible to both clinical and basic researchers. Manuscripts containing experimental data should be original data, not previously published.
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