The high-profile case of contaminated heparin last year was reason not only to consider issues relating to supply-chain integrity, but it also reminded us how critical a production process is to the quality of a drug substance. Pharmaceutical-grade heparin, a sulfated glycosaminoglycan, is derived from the mucosal tissues of slaughtered meat animals such as pig intestines, and a synthetic route has been elusive. Researchers at the Rensselaer Polytechnic Institute (RPI) report on a potentially interesting solution that may not only be valuable for producing heparin, but may also be a relevant approach for developing other biopharmaceuticals.
Using digital microfluidics, recombinant enzyme technology, and magnetic nanoparticles, Robert Lindhardt and his team at RPI created a functional prototype of an artificial Golgi organelle, which the researchers say it is the first time an artificial Golgi apparatus has been developed, according to a RPI press release. The Golgi apparatus (also just referred to as Golgi) is named after the Italian physician Camillo Golgi, who first identified it in the late 1890s. The Golgi is an organelle, similar to miniature organ in a cell, made of a network of sacs piled together into a stack. Within the natural Golgi, biomolelcules are modified posttranslationally, by undergoing glycosylation, for example, and can then be packaged for both intra-and extra- cellular distribution. Understanding how the Golgi works provides insight into how it modifies biomolecules as well as the molecule’s resulting structure and function.
The researchers’ artificial Golgi is a small microfluidics chip that simulates some of the actions of the natural Golgi’s activities, including the enzymatic modification of glycosaminoglycans. Using an inactive precursor of heparin, the researchers found that the artificial Golgi could efficiently modify the material to make it functional and suggest that an artificial Golgi could lead to a faster and safer method for producing heparin. Their work is detailed in a recent article in the Journal of the American Chemical Society (1). A recent Scientific American article further reported that Lindhart and his team hope to create a synthetic endoplasmic reticulum (ER) , the organelle in which ribosomes are located and where protein synthesis and folding takes place, and will explore the potential of integrating an artificial Golgi with the ER.
Building our understanding and broadening the availability of the “tools of the trade” in biopharmaceutical development is an important mission, and let’s hope that such efforts continue.
1. R.J. Lindhart et al., “Toward an Artificial Golgi: Redesigning the Biological Activities of Heparan Sulfate on a Digital Microfluid Chip,” J. Am. Chem. Soc. 131 (31), 11011-11048 (2009).