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Upstream processing represents a critical phase in biomanufacturing, wherein biological systems such as microorganisms, mammalian cells, or insect cells are cultivated to produce therapeutic proteins, vaccines, enzymes, or other biologically derived products. This phase encompasses all steps from the selection and genetic manipulation of the production organism to the cultivation of cells in bioreactors under tightly controlled environmental conditions.Host Selection and Genetic OptimizationThe...
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Microbial chassis selection for niche-specific engineered live biotherapeutics.

Dongmin Byun1, Li Ting Lee1, Chenxin Zhang1

  • 1NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore, Singapore; Synthetic Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; National Centre for Engineering Biology (NCEB), Singapore, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

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Selecting the right microbial chassis is key for engineered live biotherapeutic products (eLBPs). This review covers chassis for various body sites, aiding therapeutic development.

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Area of Science:

  • Microbiology
  • Biotechnology
  • Therapeutics

Background:

  • The human microbiota is crucial for health and disease modulation.
  • Engineered live biotherapeutic products (eLBPs) use modified microbes for therapeutic functions.
  • Selecting an appropriate microbial chassis is vital for eLBP efficacy and safety.

Purpose of the Study:

  • To review microbial chassis used in eLBPs for specific body niches.
  • To highlight chassis characteristics suitable for gut, skin, vagina, and tumor microenvironments.
  • To discuss strategies for enhancing eLBP colonization and identify future candidates.

Main Methods:

  • Literature review of microbial chassis in eLBP development.
  • Analysis of chassis suitability for different host niches (gut, skin, vagina, tumor).
  • Examination of strategies for improving eLBP colonization and efficacy.

Main Results:

  • Various microbial chassis are employed for specific niches, with characteristics tailored to each.
  • Chassis selection impacts eLBP survival, colonization, and therapeutic function.
  • Strategies exist to improve eLBP colonization and performance in target niches.

Conclusions:

  • Rational chassis selection is essential for durable and effective eLBPs.
  • Understanding niche-specific requirements guides the development of advanced eLBPs.
  • Emerging microbial candidates show promise for future biotherapeutic applications.