A Biomedical Engineer’s Take on Genetic Testing

Genetic testing today is mainstream, marketed to consumers who want to know where in Europe they came from or what types of hereditary diseases they could develop.

For around $200 USD you can trace your family tree to learn your origins or identify genetic abnormalities that could signal a congenital disease. James Dahlman, assistant professor in the biomedical engineering department at Georgia Tech, specializes in genetics and believes these genotyping services can be helpful, as long as they are used responsibly.

“If you’re going to start making medical predictions, you have to be careful,” said Dahlman. “Most people are not equipped to interpret statistics correctly, which can lead to negative predicting and ethical dilemmas. In a few years, genetic counselors will be in high demand so folks can make better decisions about their health.”

Dahlman is fascinated by genetics, citing gene therapy as the most interesting field in the world. Although gene therapy shows promise for treating or even preventing some of the worst diseases out there, including cancer, HIV and Parkinson’s, there are still risks involved, such as unwanted immune system reactions or inadvertently targeting the wrong cells.

That’s where Dahlman’s research comes in.


Engineering Nanoparticles

Dahlman’s lab uses nanoparticles as drug delivery vehicles, ensuring that gene therapies make it to the right place in the body. Dahlman is focused on ensuring the nanoparticles know what paths to take to reach the correct organ to start the healing process.

“The issue with genetically-engineered drugs is that they don’t work unless they get to the right cell in the body,” said Dahlman. “You can have the world’s best genetic drug that's going to fix a tumor or eradicate plaque, but it’s not going to be effective unless it travels to the right organ. In my lab, we design different nanoparticles to deliver the genetically-engineered drugs to the correct location.”

(Image courtesy of Georgia Tech.)
To that end, Dahlman has invented a testing system called FIND (Fast Identifiable Nanoparticle Delivery). During the course of identifying effective nanoparticles for drug delivery, thousands of nanoparticles must be tested, which presents scalability issues. Mice must be used for the tests because a cell plate simply can’t replicate organs in the human body.

However, researchers cannot ethically inject thousands of mice for an experiment of this magnitude. So Dahlman developed a testing system that leverages DNA barcodes (a stand-in for the actual drugs) to label each nanoparticle. Once those are injected, researchers can see where the barcodes went in the mouse.

For example, if a significant number of barcodes numbered 30 all went to the heart, Dahlman can deduce that the nanoparticle represented by barcode 30 is best suited for that organ.


Fast Identifiable Nanoparticle Delivery

“The barcode system is redefining our field because we are now able to do several really important things that we couldn’t before,” said Dahlman. “First, we can test thousands of nanoparticles at once, which has been a pipedream in our field forever. Second, we can now study the biology of drug delivery, understanding which genes affect how well a drug will work. And third, we can apply big data and artificial intelligence to drug delivery for the first time. With thousands of nanoparticles being tested at once, we can mine giant data sets for bioinformatics.”

(Image courtesy of Georgia Tech.)
Non-liver gene therapy delivery is one of the biggest challenges today that Dahlman hopes to contribute to with his work. The liver has been easier to target with gene therapy because of its filtration system; larger blood vessels let the nanoparticles pass more easily into the organ. That’s why liver diseases such as hepatitis and cirrhosis have responded well to gene therapies.

“All types of drug therapies have to be delivered,” said Dahlman. “Our field has had the best success with the liver, with 15 clinical trials already successfully running using the same nanoparticle delivery mechanism. The liver is responding extremely well to these therapies, and we are healing livers and curing people. The next frontier will be organs other than the liver, like the heart and brain with tighter blood vessel systems.”

For more nanoparticle news, check out this article to learn How to Build a Metal Nanoparticle.

Source: Georgia Institute of Technology