Drag-and-drop DNA

Photo: Pharmaceutical molecules

A collection of pharmaceutical molecules is
shown after self-assembly; © NSF

In work supported by a National Science Foundation (NSF) Small Business Innovation Research grant, researchers recently developed and began evaluating a drug for combating the lethal brain cancer glioblastoma multiforme. Now, the researchers want 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. "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 inSçquio™ with nanoscale fabrication technology.

Scientists work within inSçquio™ 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 is 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.

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.

MEDICA.de; Source: National Science Foundation (NSF)