Using a simple "drag-and-drop" computer interface and DNA self-assembly techniques, researchers have developed a new approach for drug development that could drastically reduce the time required to create and test medications.
In work supported by a National Science Foundation (NSF) Small Business Innovation Research grant, researchers fromParabon® NanoLabs of Reston, Va., recently developed and began evaluating a drug for combating the lethal brain cancer glioblastoma multiforme.
Now, with the support of an NSF Technology Enhancement for Commercial Partnerships (TECP) grant, Parabon has partnered with Janssen Research & Development, LLC, part of the Janssen Pharmaceutical Companies of Johnson & Johnson, to use the technology to create and test the efficacy of a new prostate cancer drug.
"We can now 'print,' molecule by molecule, exactly the compound that we want," says Steven Armentrout, the principal investigator on the NSF grants and co-developer of Parabon's technology. "What differentiates our nanotechnology from others is our ability to rapidly, and precisely, specify the placement of every atom in a compound that we design."
The new technology is called the Parabon Essemblix™ Drug Development Platform, and it combines their computer-aided design (CAD) software called inSēquio™ with nanoscale fabrication technology.
Scientists work within inSēquio™ to design molecular pieces with specific, functional components. The software then optimizes the design using the Parabon Computation Grid, a cloud supercomputing platform that uses proprietary algorithms to search for sets of DNA sequences that can self-assemble those components.
"When designing a therapeutic compound, we combine knowledge of the cell receptors we are targeting or biological pathways we are trying to affect with an understanding of the linking chemistry that defines what is possible to assemble," says Hong Zhong, senior research scientist at Parabon and a collaborator on the grants. "It's a deliberate and methodical engineering process, which is quite different from most other drug development approaches in use today."
With the resulting sequences, the scientists chemically synthesize trillions of identical copies of the designed molecules. The process, from conception to production, can be performed in weeks, or even days--much faster than traditional drug discovery techniques that rely on trial and error for screening potentially useful compounds.
In vivo experiments, funded by the NSF SBIR award, validated the approach, and Parabon filed a provisional patent for its methods and compounds on May 4, 2011. The final applicationwas published in 2012.
The process is characteristic of rational drug design, an effort to craft pharmaceuticals based on knowledge of how certain molecular pieces will work together in a biological system. For example, some molecules are good at finding cancer cells, while others are good at latching on to cancer cells, while still others are capable of killing cells. Working together as part of a larger molecule, these pieces could prove effective as a cancer treatment.
While there are other methods to create multi-component compounds, they generally take more time, and, most important, the majority of them lack the precise control over size, charge and the relative placement of components enabled by the new technology. The recent TECP grant provided a supplement to Parabon to support further research that will help the novel technologies meet market demands.
Via Ray and Terry's