How to Make Portable, On-Demand Biopharmaceuticals

How to Make Portable, On-Demand Biopharmaceuticals

waterJust add water.

That’s the simple but game-changing premise behind an innovative technique, developed by researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University, which allows biomolecular medicines to be produced on-site and on demand. To develop this method, which is known as “portable biomolecular manufacturing,” Wyss Institute researchers fabricated tiny, freeze-dried pellets full of enzymes and other critical cellular molecules necessary for translating DNA into proteins. When these pellets are “activated” by the addition of water, scientists can use them to cheaply, quickly, and precisely produce a range of therapeutic or diagnostic compounds.

Why is portable biomolecular manufacturing needed?

When it comes to global health, logistical challenges have long prevented critical medicines from reaching many of the people who need them most. Modern vaccines and other biomolecular compounds used to diagnose and treat medical conditions are sensitive substances, requiring constant refrigeration from the time they are synthesized to the time they are administered to a patient. In urban, industrialized areas, this presents no particular problem, but getting these medicines to remote regions that may lack established transport routes, let alone a reliable source of power for refrigeration, is much more challenging.

However, with nearly one-half of the global population living in rural areas (according to estimates from the World Health Organization), it’s a challenge that urgently needs to be addressed: for example, UNICEF has stated that in 2015, nearly 20 million infants around the world did not receive the basic vaccinations that are considered to be an essential part of a child’s healthy development.

How does portable biomolecular manufacturing work?

In the field of synthetic biology, many biomolecular medicines are produced through cell engineering, which involves modifying cells so that they perform functions outside their normal sphere of activity (like the production of drugs or biofuels). The big discovery made by the Wyss Institute researchers is that this kind of design does not necessarily have to happen within cells; it’s also possible to simply extract and freeze-dry the necessary cellular components for later reconstitution.

An earlier version of this work saw the research team using paper as a kind of host or home for these freeze-dried synthetic gene networks; but in the team’s most recent work, the cellular extracts are freeze-dried directly into two kinds of tiny pellets: one that contains the cell-free “machinery” that will produce the desired compound and one that contains DNA instructions that tell the “machinery” what product it should be manufacturing. To trigger the biomolecular manufacturing process, researchers simply need to mix the two types of pellets together and rehydrate them with water.

What are the benefits of the portable biomolecular manufacturing process?

The most significant benefit of portable biomolecular manufacturing is that its freeze-dried components are far easier to store and ship than medicines or vaccines that are already synthesized. The freeze-dried pellets are extremely stable, and can be kept at room temperature for at least a year, thereby allowing them to be transported anywhere in the world without the need for a cold-storage supply chain. This means that regions and communities that were not previously receiving important biomolecular drugs due to a lack of refrigeration capacity could soon have a new way of accessing critical medicines. In addition, the simplicity of the process means that very little training is needed to produce vital, life-saving medicines.

Another key benefit that the biomolecular manufacturing process offers is a high degree of flexibility and adaptability in drug production. The second type of pellet, the one containing the DNA instructions, can be customized to produce a number of different final products; in other words, simply by changing the “instruction manual,” the “machinery” can be directed to produce a different type of vaccine or medicine each time. This allows for responsive, on-demand production that can be a huge asset in managing outbreaks or multiple occurrences of particular health conditions.

What does the future hold for portable biomolecular manufacturing?

This innovative new process has many important, and immediate, applications. The first is simply to get critical medicines to those in need of them. Thanks to the freeze-dried pellets, clinicians working in remote or mobile medical clinics could perform vital tasks like routinely manufacturing batches of flu or tetanus shots, or quickly producing vaccines to fight emerging cases of infectious disease. Health care workers or military personnel could carry pellets in an emergency kit when going into the field. Another, more sophisticated option currently being pursued by the research team is to create “smart bandages” that contain integrated pellets; the idea is that as the bandages detect an infection, the pellets would automatically go to work producing the antimicrobial peptide needed for treatment.

The portable biomolecular manufacturing technique also shows promise as a research and educational tool. The ease and relative low cost of the approach can make it possible for researchers and educators to use biomolecular manufacturing in their work without having to have access to wet labs or sophisticated equipment. The pellets could even be used eventually to create the biotechnology equivalent of a chemistry kit, allowing students to perform synthetic biology experiments at school or at home.