Challenges in lentiviral vector production: retro-transduction of producer cell lines.

IF 4.3 3区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Frontiers in Bioengineering and Biotechnology Pub Date : 2025-05-29 eCollection Date: 2025-01-01 DOI:10.3389/fbioe.2025.1569298

Maximilian Klimpel, Christin Obert, Monica Terrao, Parameswari Singh, Haiyan Wei, Chao-Guang Chen, Andreas Gille, Silke Wissing, Holger Laux

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引用次数: 0

Abstract

The increasing demand for lentiviral vectors (LVs) has led to the development of several stable cell lines and production methods over the last 2 decades in order to increase titers and yields, reduce production costs and improve the safety of the vector product. However, the phenomenon of retro-transduction, which describes the transduction of LV producer cells by self-produced LVs, remains largely unaddressed in the context of LV production. Recent research has focused on various approaches to reduce the impact of retro-transduction on LV yield and process performance. This article reviews existing and new research data that highlights the impact of retro-transduction in LV manufacturing. In addition, a perspective on current advances to reduce retro-transduction is provided and a potential novel strategy called ENV-Y is presented, which could not only reduce the impact of retro-transduction but also facilitate the subsequent LV downstream process.

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慢病毒载体生产的挑战：生产细胞系的逆转录转导。

在过去的20年里，对慢病毒载体（LVs）的需求不断增加，导致了几种稳定的细胞系和生产方法的发展，以提高滴度和产量，降低生产成本并提高载体产品的安全性。然而，在LV产生的背景下，逆转录转导现象（描述了自产LV对LV产生细胞的转导）在很大程度上仍未得到解决。最近的研究集中在各种方法来减少反向转导对LV产率和工艺性能的影响。本文回顾了现有的和新的研究数据，强调了逆转录转导在LV制造中的影响。此外，本文还对当前减少逆转录转导的进展进行了展望，并提出了一种称为ENV-Y的潜在新策略，该策略不仅可以减少逆转录转导的影响，还可以促进后续的LV下游过程。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Bioengineering and Biotechnology Chemical Engineering-Bioengineering

CiteScore

8.30

自引率

5.30%

发文量

2270

审稿时长

12 weeks

期刊介绍： The translation of new discoveries in medicine to clinical routine has never been easy. During the second half of the last century, thanks to the progress in chemistry, biochemistry and pharmacology, we have seen the development and the application of a large number of drugs and devices aimed at the treatment of symptoms, blocking unwanted pathways and, in the case of infectious diseases, fighting the micro-organisms responsible. However, we are facing, today, a dramatic change in the therapeutic approach to pathologies and diseases. Indeed, the challenge of the present and the next decade is to fully restore the physiological status of the diseased organism and to completely regenerate tissue and organs when they are so seriously affected that treatments cannot be limited to the repression of symptoms or to the repair of damage. This is being made possible thanks to the major developments made in basic cell and molecular biology, including stem cell science, growth factor delivery, gene isolation and transfection, the advances in bioengineering and nanotechnology, including development of new biomaterials, biofabrication technologies and use of bioreactors, and the big improvements in diagnostic tools and imaging of cells, tissues and organs. In today`s world, an enhancement of communication between multidisciplinary experts, together with the promotion of joint projects and close collaborations among scientists, engineers, industry people, regulatory agencies and physicians are absolute requirements for the success of any attempt to develop and clinically apply a new biological therapy or an innovative device involving the collective use of biomaterials, cells and/or bioactive molecules. “Frontiers in Bioengineering and Biotechnology” aspires to be a forum for all people involved in the process by bridging the gap too often existing between a discovery in the basic sciences and its clinical application.