Project Grant R41TR005278

Award Date 7/1/24
Completion Date 6/30/25
Dollars Obligated $350K
Federal Grant Program
93.350
Assistance Type
Project Grant
Place of Performance
Massachusetts, USA
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This $350,000 Project Grant award from the National Center for Advancing Translational Sciences (NCATS), under the 93.350 CFDA program, supports the development of the Codomax EPI-MAX platform. This integrated omics and computational technology leverages cellular stress responses to enhance the production of difficult-to-express therapeutic proteins, with a focus on improving secretion and preventing aggregation in the Pichia pastoris expression system. The key products or services to be delivered include:

  1. Applying the EPI-MAX platform to engineer Pichia strains with optimized expression of chaperone proteins like Kar2, Calnexin, and Protein Disulfide Isomerase to enhance secretion of a model recombinant protein, human Interleukin-2.

  2. Utilizing CRISPR-Cas9 to replace native chaperone genes with stress codon-engineered variants, and overexpressing the tRNAs responsible for decoding these optimal stress codons.

  3. Assessing intracellular protein aggregation and proper folding using limited proteolysis-coupled mass spectrometry.

Successful completion of this Phase I project will demonstrate the versatility of the EPI-MAX platform in addressing protein production bottlenecks and generate designer Pichia strains, optimized gene sequences, and CRISPR-Cas9 tools to enable efficient manufacturing of challenging biologic therapeutics.

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