The development of a bioengineered heparin from a non-animal source is in response to a health crisis that took place in early 2008. This crisis involved the introduction of an oversulfated chondroitin sulfate into heparin produced from hogs in China leading to the death of nearly 100 Americans. Recent research in our laboratories suggests that it is now possible to prepare a bioengineered heparin from non-animal sources using fermentation combined with chemoenzymatic methods. The proposed 5-year project is a translational and multi-disciplinary research effort involving the Rensselaer Polytechnic Institute, University of North Carolina and Albany College of Pharmacy, aimed at producing kilogram quantities of non-animal sourced bioengineered heparin. By controlling the process steps this bioengineered heparin will be prepared with a structure identical to the pharmaceutical heparin prepared from animals. Both chemical and bioequivalence studies will provide the necessary pre-clinical data required to carry bioengineered heparin forward as a generic heparin. The results of this 5-year translational bioengineering research project will be the synthesis of 1 kilogram of non-animal sourced heparin, which serves as a well defined deliverable that is chemically and biologically equivalent to USP heparin. A second well-defined deliverable will be an optimized and cost effective process that can be used ultimately to generate bioengineered, non-animal heparin at scales sufficient to satisfy the therapeutic needs in the US. This material and the accompanying process will be made available to both large and small business partners interested in moving this bioengineered heparin into human clinical trails as a novel and safer replacement for animal sourced heparin. We hypothesize that application of recombinantly-expressed biosynthetic enzymes in a well controlled process can afford a bioengineered heparin that is the generic equivalent of USP heparin. Furthermore, we envision that this bioengineered heparin will be safer for patients and can be prepared at costs competitive to heparin obtained from animal tissues. There are four specific aims of this proposal. 1. Optimize the production of bioengineered heparin;2. Confirm chemical equivalence of bioengineered heparin with USP heparin;3. Confirm bioequivalence of bioengineered heparin with USP heparin;and 4. Scale-up and produce a kilogram of bioengineered heparin while maintaining chemical and bioequivalence.
The proposed effort impacts human health by developing a process to prepare a bioengineered heparin that is chemically and biologically equivalent to pharmaceutical heparin currently prepared from pig intestine. This process will improve the safety and uniformity of heparin and prevent future contamination or adulteration of this important drug that is administered to several hundred thousand patients each day in the US.
|Fu, Li; Suflita, Matthew; Linhardt, Robert J (2016) Bioengineered heparins and heparan sulfates. Adv Drug Deliv Rev 97:237-49|
|Liu, Z; Sun, X; Cai, C et al. (2016) Characteristics of glycosaminoglycans in chicken eggshells and the influence of disaccharide composition on eggshell properties. Poult Sci 95:2879-2888|
|Rubinson, Kenneth A; Chen, Yin; Cress, Brady F et al. (2016) Heparin's solution structure determined by small-angle neutron scattering. Biopolymers 105:905-13|
|Sun, Xiaojun; Lin, Lei; Liu, Xinyue et al. (2016) Capillary Electrophoresis-Mass Spectrometry for the Analysis of Heparin Oligosaccharides and Low Molecular Weight Heparin. Anal Chem 88:1937-43|
|Li, Guoyun; Li, Lingyun; Xue, Changhu et al. (2015) Profiling pneumococcal type 3-derived oligosaccharides by high resolution liquid chromatography-tandem mass spectrometry. J Chromatogr A 1397:43-51|
|Mora-Pale, Mauricio; Bhan, Namita; Masuko, Sayaka et al. (2015) Antimicrobial mechanism of resveratrol-trans-dihydrodimer produced from peroxidase-catalyzed oxidation of resveratrol. Biotechnol Bioeng 112:2417-28|
|Li, Guoyun; Li, Lingyun; Tian, Fang et al. (2015) Glycosaminoglycanomics of cultured cells using a rapid and sensitive LC-MS/MS approach. ACS Chem Biol 10:1303-10|
|FarrÃ¡n, Angeles; Cai, Chao; Sandoval, Manuel et al. (2015) Green solvents in carbohydrate chemistry: from raw materials to fine chemicals. Chem Rev 115:6811-53|
|Jasper, John P; Zhang, Fuming; Poe, Russell B et al. (2015) Stable isotopic analysis of porcine, bovine, and ovine heparins. J Pharm Sci 104:457-63|
|Fu, Li; McCallum, Scott A; Miao, Jianjun et al. (2015) Rapid and accurate determination of the lignin content of lignocellulosic biomass by solid-state NMR. Fuel (Lond) 141:39-45|
Showing the most recent 10 out of 89 publications