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

Cerini, Fabrice; Gaertner, Hubert François; Madden, Knut; Tolstorukov, Ilya; Brown, Scott; Laukens, Bram; Callewaert, Nico; Harner, Jay C; Oommen, Anna M; Harms, John T; Sump, Anthony R; Sealock, Robert C; Peterson, Dustin J; Johnson, Scott K; Abramson, Stephan B; Meagher, Michael; Offord, Robin Ewart; Hartley, Oliver

doi:10.1016/j.pep.2015.10.011

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Title		A scalable low-cost cGMP process for clinical grade production of the HIV inhibitor 5P12-RANTES in Pichia pastoris
Authors		Cerini, Fabrice Gaertner, Hubert François Madden, Knut Tolstorukov, Ilya Brown, Scott Laukens, Bram Callewaert, Nico Harner, Jay C Oommen, Anna M Harms, John T Sump, Anthony R Sealock, Robert C Peterson, Dustin J Johnson, Scott K Abramson, Stephan B Meagher, Michael Offord, Robin Ewart Hartley, Oliver show all authors [1 - 18]
Published in		Protein Expression and Purification. 2016, vol. 119, p. 1-10
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.
Identifiers		DOI: 10.1016/j.pep.2015.10.011 PMID: 26506568
Full text		Article (Published version) (845 Kb) - Free access
Structures		Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie
Research group		Hiv (835)
Citation (ISO format)		CERINI, Fabrice et al. A scalable low-cost cGMP process for clinical grade production of the HIV inhibitor 5P12-RANTES in Pichia pastoris. In: Protein Expression and Purification, 2016, vol. 119, p. 1-10. doi: 10.1016/j.pep.2015.10.011 https://archive-ouverte.unige.ch/unige:88663