Bulk production of the antiviral lectin griffithsin

Fuqua, Joshua L.; Hamorsky, Krystal; Khalsa, Guruatma; Matoba, Nobuyuki; Palmer, Kenneth E.

Differential scanning fluorimetry (DSF) requires additional excipients in the formulation and adds another layer of complexity, while direct modification of the amino acid sequence requires confirmation of the activity, structural stability, safety and potential modifications to the manufacturing process. In our work with GRFT, protein oxidation is and continues to be a potential concern because the amino acid sequence contains multiple potentially oxidizable amino acids (Figure 3 ). Scaled manufacture in conjunction with long-term storage is a variable not generally simulated in the laboratory. Multiple contingency plans have been discussed, and preliminary data have been collected in an effort to preemptively resolve issues related to oxidation of GRFT. Alternative amino acid sequences, reducing the number of oxidizable amino acids, have been developed that would provide oxidation resistance, and formulations addressing oxidation protection are under development. These options are all being developed concurrently as contingencies for oxidation. The need for an alternative API or formulation has not been established in the field, but successful clinical development will require any issues with oxidation be resolved.