For Research Use Only. Not for Clinical Use.

Homo-amino-acid polymer (HAP) is a synthetic polypeptide containing a regular amino acid sequence, constantly consisting of repeated sequences rich in hydrophobic amino acids. Fusion of pharmaceutical protein with the optimized HAP sequences by genetic engineering modified should improve drug pharmacokinetic. This technique can easily obtain uniform HAP modified protein molecules and has a broad commercial prospect. Based on our rich experience, well-established platform, and excelsior attitude, Creative Biolabs can screen HAPs of various lengths and types to prolong the half-life of target drugs while maintaining potency and ultimately bring your product to market.

Introduction of HAPylation Based Half-Life Extension

Compared with common plasma proteins, most proteins of pharmaceutical interest have a small size below the threshold value for kidney filtration, which lead to rapid clearance and a very short half-life of less than 1h, especially in recombinant antibody. Attachment of the HAPs to protein therapeutics increases their hydrodynamic radius and molecular weight, making them less prone to kidney filtration. Repeated sequence of a hydrophobic amino acid rich polypeptide is the active molecule of HAPylation, while glycine is usually chosen due to the lack of a side chain. However, charged amino acids should be introduced into HAP sequence to increase the solubility.

Different from the traditional half-life extension strategy, HAPylation based half-life extension adopts recurrent hydrophobic polypeptide as active site, which is bio-degradable, non-toxic, non-immunogenic and cost-effective. Furthermore, purified protein drug molecules can be obtained in this method avoiding additional in vitro chemical modification processing, which is in conformity with the principle of Good Manufacturing Practice.

Fig.1 Schematic representation of HAPylation based half-life extension with a therapeutic protein. (Zelikin, 2016)

Applications of HAPylation Based Half-Life Extension

HAPylation based half-life extension is a novel technology discovered in 2007 and is mainly aimed at promoting the half-life of pharmaceutical protein with small molecular weight. A research team modified Fab fragment of the clinically approved therapeutic antibody with glycine-rich HAPs of different lengths and extended its in vivo half-life in mice by more than three times. Further characterization supported that HAPylation-antibody enhanced hydration volume while maintaining its bioactivity and proper folding, as expected. This result demonstrates the feasibility of HAPylation based half-life extension, and further optimization of the sequence and length of HAP can theoretically extend the half-life of recombinant pharmaceutical proteins.

Highlights of HAPylation Based Half-Life Extension Service

• Simplicity, inexpensive, and rapidly.
• Avoiding chemical modification, good biocompatibility and more appropriate.
• Suitable for almost all recombinant pharmaceutical proteins.
• Do not impact the biological activity.

HAPylation Based Half-Life Extension Service introduces a shortcut to extend the in vivo half-time of proteins rapidly and inexpensively. It provides a new idea for therapeutic proteins production. This method has been widely used in recombinant antibody fragments, hormones, and interferons modification to promote them into clinical research. If you are interested in our half-life extension service, please feel free to contact us for more information.

Reference

1. Zelikin, A. N.; et al. Materials and methods for delivery of biological drugs. Nature Chemistry. 2016, 8(11), 997-1007.