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Automated Acoustic Dispensing for the Serial Dilution of Peptide Agonists in Potency Determination Assays
Published on: November 10, 2016
Development and characterization of a long-acting recombinant hFSH agonist
1Department of Obstetrics and Gynecology and Center for Reproductive Sciences, School of Public Health, Columbia University, New York, NY 10032, USA.
Human Reproduction (Oxford, England)
|January 15, 2003
Summary
This study developed a novel recombinant human follicle-stimulating hormone (rhFSH) analogue, rhFSH-N2, with enhanced N-linked glycosylation. The new analogue demonstrated a prolonged half-life and increased in vivo bioactivity, suggesting potential clinical benefits.
Area of Science:
- Biotechnology
- Endocrinology
- Glycobiology
Background:
- Recombinant human follicle-stimulating hormone (rhFSH) is crucial for fertility treatments.
- Modifying rhFSH glycosylation can alter its pharmacokinetic and pharmacodynamic properties.
- Previous strategies involved fusing hCG's carboxyterminal peptide (CTP) to create follitropin agonists.
Purpose of the Study:
- To engineer and evaluate a novel rhFSH analogue (rhFSH-N2) with additional N-linked glycosylation.
- To assess the in vitro bioactivity, pharmacokinetics, and in vivo efficacy of rhFSH-N2 compared to native rhFSH.
Main Methods:
- A DNA construct encoding rhFSH with two N-oligosaccharide signal sequences was created and expressed in CHO-K1 cells.
- In vitro bioactivity was measured by cAMP induction in CHO cells expressing the hFSH receptor.
- Pharmacokinetics were determined in rats, and in vivo bioactivity was assessed by ovarian weight gain.
Main Results:
- rhFSH-N2 exhibited comparable in vitro bioactivity to native rhFSH.
- The half-life (t1/2) of rhFSH-N2 was significantly prolonged (7.3 h) compared to native rhFSH (3.7 h).
- rhFSH-N2 treatment resulted in significantly greater ovarian weight gain in rats compared to native rhFSH and saline controls.
Conclusions:
- rhFSH-N2 possesses an extended half-life and enhanced in vivo bioactivity relative to native rhFSH.
- This engineered rhFSH analogue, featuring additional N-oligosaccharides, holds promise for improved clinical applications in reproductive medicine.
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