A scalable low-cost cGMP process for clinical grade production of the HIV inhibitor 5P12-RANTES in Pichia pastoris.

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  • Additional Information
    • Source:
      Publisher: Academic Press Country of Publication: United States NLM ID: 9101496 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-0279 (Electronic) Linking ISSN: 10465928 NLM ISO Abbreviation: Protein Expr Purif Subsets: MEDLINE
    • Publication Information:
      Publication: Orlando, FL : Academic Press
      Original Publication: San Diego : Academic Press, c1990-
    • Subject Terms:
      Pichia*; Anti-HIV Agents/*metabolism ; Chemokines, CC/*biosynthesis ; HIV/*drug effects ; HIV Infections/*drug therapy; Anti-HIV Agents/isolation & purification ; Anti-HIV Agents/pharmacology ; Bioreactors/economics ; Bioreactors/standards ; Chemokines, CC/isolation & purification ; Chemokines, CC/pharmacology ; Chromatography, High Pressure Liquid ; Chromatography, Ion Exchange ; Fermentation ; Humans ; Inhibitory Concentration 50 ; Pilot Projects ; Virus Internalization/drug effects
    • Abstract:
      In the continued absence of an effective anti-HIV vaccine, approximately 2 million new HIV infections occur every year, with over 95% of these in developing countries. Calls have been made for the development of anti-HIV drugs that can be formulated for topical use to prevent HIV transmission during sexual intercourse. Because these drugs are principally destined for use in low-resource regions, achieving production costs that are as low as possible is an absolute requirement. 5P12-RANTES, an analog of the human chemokine protein RANTES/CCL5, is a highly potent HIV entry inhibitor which acts by achieving potent blockade of the principal HIV coreceptor, CCR5. Here we describe the development and optimization of a scalable low-cost production process for 5P12-RANTES based on expression in Pichia pastoris. At pilot (150 L) scale, this cGMP compliant process yielded 30 g of clinical grade 5P12-RANTES. As well as providing sufficient material for the first stage of clinical development, this process represents an important step towards achieving production of 5P12-RANTES at a cost and scale appropriate to meet needs for topical HIV prevention worldwide.
      (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)
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    • Grant Information:
      090561 United Kingdom Wellcome Trust; 104252 United Kingdom Wellcome Trust
    • Contributed Indexing:
      Keywords: 5P12-RANTES; Biopharmaceutical; CCR5; Chemokine; HIV; Microbicide; Pichia; Process development; Yeast; cGMP
    • Accession Number:
      0 (5P12-RANTES)
      0 (Anti-HIV Agents)
      0 (Chemokines, CC)
    • Publication Date:
      Date Created: 20151028 Date Completed: 20161024 Latest Revision: 20181113
    • Publication Date:
      20231215
    • Accession Number:
      PMC4725576
    • Accession Number:
      10.1016/j.pep.2015.10.011
    • Accession Number:
      26506568