Augmented super-soldiers, self-healing materials used in cars and airplanes and using genetic engineering to fight off infections sound like things straight out of science fiction. And they are, for now.
Even the humblest bacterium is an expert at sensing, responding to and manipulating its environment, says Casalnuovo. But, living things are quite fragile and can be killed by changes in the environment, including temperature, pressure,
By bringing together biologists, chemists,
Slice and dice pathogenic invaders
Using porous silica nanoparticles to deliver a powerful new genetic engineering tool, CRISPR (clustered regularly interspaced short palindromic repeats), to where it needs to act, the NanoCRISPR team hopes to slice-and-dice the genome of invaders for public health and biodefense.
Unlike previous genetic engineering tools, such as zinc-finger nucleases or TALEN constructs, the CRISPR system is more adaptable, more precise and has transformed biology since major advances in 2012. Like previous genetic engineering tools, however, the CRISPR system by itself cannot target and enter cells and is thus ineffective without a delivery system.
That’s where the nanoparticles come in, says Casalnuovo. They can envelop and protect the delicate complex as it travels through the body. The outside of the nanoparticle can be coated with signaling molecules that camouflage the particle and direct it to the right place, such as the invading pathogen or specific organs and tissues targeted by the pathogen.
Sasaki says they have made great strides in encapsulating the biological cargo in the nanoparticles, deliver-ing the cargo to model cells and triggering a genetic change. Through computer modeling, cellular assays and animal model studies, they hope to develop CRISPR-based countermeasures for the Zika virus and a drug-resistant bacterium.
Sandia’s previous encapsulation work involved much smaller drug molecules such as antibiotics. Casalnuovo says CRISPR’s protein-RNA complex is larger, more complex, more sensitive to the environment and needs to be delivered more precisely than the previous drug molecules.
Immune systems of the future
The next step for the
Another possible path forward focuses on adapting the immune response in biological systems to make human-designed systems more robust. Many systems, from algae ponds grown for biofuels to mechanical structures, would benefit from the ability to recognize when things deviate from normal, learn from past experience, and initiate a repair, says Casalnuovo.
By fully understanding how nature employs biological design rules, researchers can improve non-biologic components, better interface the living and non-living systems and engineer the hybrid systems, Casalnuovo says.
“This is a hard problem from a lot of different perspectives. This Research Challenge is a 10- or 20-year effort, maybe even 50 years of work, with the potential for some really transformative things,” says Casalnuovo. “This work has the potential to change the way we live.”