Harnessing Viral Capsid Self-Assembly Capabilities for Better Drug Delivery
Viruses have played con-man to tissues and immune systems for a long time. By harnessing these capabilities, researchers are attempting to create nanoreactors and better therapeutic vehicles. Image Source: Wikimedia Commons User Splette
Viruses are a non-living anomaly in the microscopic world; they make a living out of hijacking a cell or organism’s inner machinery to reproduce and spread, rather than reproducing on their own. One of many viruses’ particularly impressive accomplishments is their ability to target specific tissues and cross the blood brain barrier, something which scientists have struggled to do for years. Why not use viruses’ technology to benefit patients?
Recently, researchers have designed a viral capsid-like self-assembling protein shell that may be able to target and deliver drugs to specific tissues and systems within the human body. This may allow researchers—and their drugs—to evade first pass metabolism and accurately direct them towards their destination. Modern lab software will help scientists delve further into this technology and better investigate how systems and tissues within the body interact with these capsids.
Viral Capsids in a Protein Shell
Many viruses encase their genetic materials in a capsid, an icosahedral protein shell. The icosahedral shell is a commonly observed structure, indicating that it confers a high survival rate. When a capsid bursts outside of host cells it loses its infectivity, which means that it is unable to proliferate; however, if it delivers its payload of genetic material to a host cell, it lives to see the expansion of its tiny viral empire.
Custom designing a self-assembling protein shell into well-defined complexes is a promising route towards macromolecular machines and better ways to develop temperamental biological therapeutics. In the case of viruses, these shells are self-assembling, which generally means they are composed of a number of subunits that systematically interconnect themselves into a sealed vehicle. In attempts to mimic this process, scientists have been utilizing metals, disulfide bonds, genetic fusions and ideal helix-helix interactions. The results have been consistently inconsistent, yielding unpredictable structures, but recent advances in lab software have allowed researchers to accurately develop small volume—yet stable and predictable—nanocages.
By assessing existing stable structures, icosahedral protein assemblies were designed from known trimeric protein scaffolds. Modern lab software assisted researchers in compiling the genes encoding these designs, allowing for them to be assembled from oligonucleotides and cloned into E. coli. This led to scientists creating a number of potential protein capsids that were a great improvement over previous successes in terms of volume available. The I3-01 icosahedron that the scientists designed is exceptionally stable, and the genetic code used to generate it is robust.1
This technology may assist medications that struggle to survive first pass metabolism. With recent innovations in lab software, research and development in the realm of biologics to treat illnesses is gaining steam. For example, antibodies therapies are all the rage, but they are difficult to deliver as they generally are delivered via IV on a very regular basis. What if physicians were able to send patients home with a bottle of pills, that had few side effects, and were able to check on them weeks or months later? This would likely increase compliance, reduce therapeutic cost and reduce the strain on the healthcare system, dramatically.
Biologic Nanoreactors and Medication Vehicles
This development opens the floodgates to a whole new world of possibilities that closely resemble science fiction. In the supplementary material of their academic paper, these scientists go into some detail about how these manufactured protein shells can function as nanoreactors. The researchers encapsulated 2-dehydro-3-deoxy-phosphogluconate (KDPG) aldolase within the I3-01 structure and were able to report that it showed native enzymatic activity. Moving forward, this could be coupled with a number of different enzymes to manufacture biologic therapeutics en route to the targeted tissue.
These enzymes could be enzymes that are already known to be efficacious in certain disorders that are naturally depleted or lack the ability to accurately focus on one type of tissue. Take Gaucher Disease, for example. Gaucher Disease is an illness that leads to the accumulation of fatty molecules called cerebrosides in the body’s organs and tissues. Using this innovative technology, the native enzymes inherently depleted by the disease could be enclosed and transported to target areas. Currently, enzyme replacement therapy is available for Gaucher Disease, but researchers struggle to find a way to target specific tissues affected by this disease. With the aid of modern lab software, scientists could design and give the I3-01 a peptide or genetic tail that would allow it to “stick” only to specific tissues.
Scientists are expanding their knowledge of many rare, and previously untreatable, diseases. As they continue to do so more therapeutic solutions are being developed; however, many of these therapeutics fall flat well before they reach clinical trials. For many of them, it’s due to an inability to penetrate the affected tissues and evade the body’s immune and digestive systems. By using innovative lab software to design therapeutics in a way that they can be encapsulated in a protein shell and delivered to specific tissues using a genetic, antibody or peptide tag, more of these newly developed biologics may survive through to the end of the development process. The further researchers are able to go, the more they will learn and the closer they will get to cures.
Modern lab software can help researchers decipher results from various stages and funnel those results into better development of therapeutics and of protein shells themselves. For example, initiating comprehensive data mining at the point of discovery and then feeding that gleaned information into predictive analytic software, researchers can conduct in silico simulations, saving time and money spent at the bench.
The need for therapeutic solutions in many of these rare diseases is imminent. From where researchers currently stand, there is a multitude of possibilities. However, this technology is still in its infancy. Innovative lab software is going to be the key to moving understanding and technology forward. BIOVIA Biologics is a suite of capabilities supported by a common platform, designed to help with the discovery and optimization of biotherapeutic candidates, as well as assess the nanoreactor and drug vehicle capabilities of new protein shells. With key capabilities like workflow support and predictive analytics, assessing data and designing complementary therapeutics will be faster and more efficient. Please contact us today to learn more about how our software options can support the efforts of your lab.
- “Design of a hyperstable 60-subunit protein icosahedron,” July 7, 2016, http://www.nature.com/nature/journal/v535/n7610/full/nature18010.html ↩