Maximilian Klimpel, Christin Obert, Monica Terrao, Parameswari Singh, Haiyan Wei, Chao-Guang Chen, Andreas Gille, Silke Wissing, Holger Laux
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Challenges in lentiviral vector production: retro-transduction of producer cell lines.
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.
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.