Researchers Propose a Portable Biomolecular Manufacturing Method

A group of researchers from the Wyss Institute for Biologically Inspired Engineering at Harvard University say they have developed a potential method that could assist in the transportation and production of temperature-sensitive pharmaceuticals at a reduced cost. The study, published on Sept. 22, 2016 in Cell, discusses using freeze-dried pellets that can create complex compounds with the addition of water.

Instead of freeze drying molecules and rehydrating them, researchers demonstrate the potential to freeze-dry specific molecular machinery that can later be used in the transcription and translation processes. Once water is added to the pellets and the compounds are created, they can be administered to patients in several forms including injection, oral doses, and topically. The researchers assert this method provides a cost-effective alternative to some cold chain solutions, which they say can account for up to 80% of a vaccine’s total cost.

Keith Pardee, PhD, study author and assistant professor of Pharmacy at the University of Toronto, told BioPharm International this is important because this method could potentially be used to transport therapeutics that typically rely on the cold chain to patients at a reduced cost. This study is based off work done by the same researchers in 2014, Pardee said, using “freeze-dried paper-based cell-free reactions to deploy synthetic gene networks outside of the lab in a sterile and abiotic format.”

This new study, titled “Portable, On-Demand Biomolecular Manufacturing,” focused specifically on the production of an antigen for diphtheria. The researchers manufactured the equivalent of 33 human doses of the antigen at a cost of between $10.54 and $18.41 per dose. They then demonstrated the efficacy of the drug using a mouse model. Pardee noted conducting research with the diphtheria antigen was ideal, because these vaccines do not need to be frozen.

“With this approach, we have the potential to solve this challenge by distributing the freeze-dried manufacturing capacity rather than the product itself. This has the added benefit of reducing transportation costs as no refrigeration is required and the majority of the weight in the form of water has been eliminated,” Pardee said. “Furthermore, storage at ambient temperatures reduces infrastructure burden. When the need arises, reaction pellets and DNA encoding the manufacturing instructions (gene constructs) can be simply hydrated for on-site and on-demand synthesis.”

Pardee also said this method can improve patient access to personalized therapeutics, vaccines in the event of an outbreak, and protein-based diagnostic tools. This is particularly relevant for patients living in remote locations, that may not have the access to therapeutics that require cold-chain transport. Earlier this year, Pardee continued, the researchers used this method to “develop diagnostics for the Zika virus that could detect viral RNA at clinically relevant concentrations.”

The researchers note there may be a need for additional research into scalability for molecules that may not be amendable to freeze drying. But Pardee says the team is optimistic. “Going forward we expect advances in the field of cell-free expression to continue to improve yield and there are also exciting technologies in the area of vaccine delivery that promise to reduce the amount of material required for immunization,” he said.

Source: Cell, Wyss Institute