Synthesis and Biological Activity Assessment of Different Diastereomers in siRNA Drug LEQVIO (Inclisiran) (U01) Clinical Trial Not Allowed
This research will synthesize and test individual forms of the siRNA drug LEQVIO to understand how each form contributes to the drug's overall effectiveness.
Funder: Food and Drug Administration
Due Dates: Forecasted (no due date announced)
Funding Amounts: $300,000 (single award; cooperative agreement)
Summary: Supports research to synthesize and assess the biological activity of individual diastereomers in the siRNA drug LEQVIO (Inclisiran) to inform drug quality and regulatory science.
Key Information: This is a forecasted opportunity; application details and deadlines are not yet posted.
Description
This funding opportunity, offered by the Food and Drug Administration (FDA), aims to advance regulatory science by supporting research on the stereochemical composition and biological activity of LEQVIO (Inclisiran), an FDA-approved, GalNAc-conjugated siRNA drug. The project will:
- Synthesize each diastereomer of LEQVIO in stereochemically pure form.
- Assess the biological activity of each pure diastereomer in inhibiting PCSK9, using both in vitro assays and a transgenic mouse model.
- Develop analytical methods to identify and characterize the stereochemical structure of each diastereomer.
- Evaluate the individual contribution of each diastereomer to the overall pharmacological activity of LEQVIO.
The tools and knowledge developed through this research are expected to be applicable to other GalNAc-conjugated siRNAs and siRNA drugs in general, contributing to the evaluation of generic siRNAs and the quality control of oligonucleotide therapeutics.
