AI Article Synopsis
- Optimizing the druggability of bioactive proteins is essential to enhance their therapeutic effects, focusing on improving pharmacokinetic properties without losing biological activity.* -
- The study introduces a new platform called lipidation-dimerization (LiDi) that combines lipidation and a dimeric form of Fibroblast growth factor 21 (FGF21), a hormone with potential for treating non-alcoholic steatohepatitis (NASH).* -
- In vivo tests show that the LiDi FGF21 analogs provide better pharmacokinetic properties and efficacy for NASH compared to existing treatments, effectively prolonging therapeutic effects while maintaining activity.*
Article Abstract
Optimizing the druggability of both native and AI-designed bioactive proteins is crucial for realizing their therapeutic potential. A key focus in designing protein-based therapeutics is improving their pharmacokinetic properties. However, a significant challenge is to preserve biological activity while implementing long-acting strategies. Fibroblast growth factor 21 (FGF21), an endogenous hormone with potential as a treatment for non-alcoholic steatohepatitis (NASH), exemplifies this challenge. In this study, we present a novel lipidation-dimerization (LiDi) platform that integrates lipidation with a dimeric form of FGF21 connected by a hydrophilic linker. The lipidation enhances albumin binding, enabling sustained release, while the dimeric structure boosts biological activity. In vivo evaluations of the LiDi FGF21 analogs demonstrated that they offer excellent pharmacokinetic properties and superior efficacy compared to other treatments for NASH. This platform effectively extends the therapeutic half-life of proteins without compromising their activity, substantially broadening the application range of proteins as therapeutics.
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| http://dx.doi.org/10.1016/j.jconrel.2024.11.006 | DOI Listing |
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