Securing High Quality Engineered Cells with Novel Biological Security Technology

The Centers for Disease Control and Prevention, the Department of Homeland Security, and other authorities have reported a record number of illegal shipments of organic goods. At the same time, the world’s intelligence community has noticed many attempts to smuggle sensitive biological samples in attempts at industrial theft or espionage.

Corey Wilson, PhD, a professor in Georgia Tech’s School of Chemical and Biomolecular Engineering (ChBE) said: “A small bottle of genetically engineered cells can contain multi-million dollar intellectual property and require several years of work to develop”. Therefore, the protection of high-quality cells has become very important in the biotechnology industry.

Wilson and his team published their study “Protecting cells at the genetic level and simulating unauthorized access through a biohackathon” Advances in Science to demonstrate the effectiveness of their new biosecurity technology, known as GeneLock™, in protecting high-quality engineered cells.

GeneLock is described as a cybersecurity-inspired technology that protects important genes directly at the DNA level. To demonstrate its power, Wilson’s team conducted what they describe as a first-of-its-kind biohackathon to simulate unauthorized access.

“GeneLock greatly improves our ability to protect high-quality cells by extending protection from the lab environment to the genome,” said Wilson.

Economic impact

Some estimates put the global market for genetic materials at more than $1.5 trillion, which is estimated to reach $8 trillion by 2035. Uses of these materials range from advanced medicines and enzymes for material research to specialty chemicals and durable materials.

Currently, the protection of high-quality cell lines is based on physical security such as restricted access to the lab and secure equipment.

Wilson explains: “The main weakness of physical security measures has been avoidance, often there are no measures to protect important cells from theft, abuse, or unauthorized use.

Once the sample leaves the building, the DNA it carries remains fully functional. This is like putting an unlocked cell phone in a desk drawer. “Anyone who can get into the drawer can look at important information on the phone—or in this case, access the entire cell phone.”

The GeneLock biological security technology developed by Wilson and his team places a password on engineered cells, similar to those used in ATM machines and secure cell phones.

Instead of leaving the important genes in readable form, the team breaks down the DNA sequence of interest. The deleted genetic material remains in an inactive state unless the host cell receives the correct sequence of chemical inputs. That information acts as a molecular password.

“Only the right combination, given in the right order, rearranges the DNA into a functional structure,” says Wilson.

Biohackathon security testing

To test the technology, the researchers organized a blue team and a red team in what they describe as an ethical biohackathon. The blue team sequenced the hidden DNA, while the red team was challenged to find the correct chemical passcode by experimenting with a gray box exercise, meaning the red team had partial knowledge of the system but did not have access to the internal architecture.

“This method of testing security is often used in cybersecurity,” says Wilson.

The blue team created the system internally E. coli. The protected asset was a type of fluorescent protein identified as a measurable site for important commercial targets. When the correct chemical sequence was used, fluorescence was turned on. Without the correct passcode, the gene remained blocked and the cells could not fluoresce green.

Wilson continues: “In fact, many DNA sequences reveal important proteins or chemicals that are not actually visible to the human eye, requiring special equipment or tests to be detected.” “If the biohackathon had been done with an important business goal, the penetration test would have taken 10 times longer to complete, years instead of months.”

The results of the biohackathon showed a significant reduction in risk. GeneLock has reduced the chance of unlocking a genetic treasure through a random search to one in 85,000 (0.001 chance), assuming an unauthorized user has access to the necessary chemical resources.

Without access to those supplements, “the chance of success suddenly becomes illogical,” says Dowan Kim, PhD, lead author of the study.

What follows

Although the researchers used a non-commercial fluorescent protein as a test case, they say the implications extend far beyond that. Many biotech companies rely on engineered species. New England Biolabs, for example, produces more than 265 unproduced enzymes E. colieach represents a cell line of higher quality, depending on the group.

Protein-based drugs are also made in living cells, and metabolic pathways are used to produce unique chemicals, bioplastics and high-quality compounds.

“In everything, the genetic structure in the cell represents the intellectual property that can be protected by our technology,” says Ishita Kumar, PhD candidate at ChBE and co-author of the study.

Although the team’s current goal is to protect intellectual property in the form of high-quality cells, future iterations aim to strengthen biological protection in general.

“We are currently developing safeguards to minimize the unauthorized use or release of sensitive cells that could be harmful to human health or the environment,” says Wilson.