ResearchUNC Charlotte

Charlotte Researcher Kirill Afonin Helping To Revolutionize Gene Therapy

By ANNA HOLT

Photography by KAT LAWRENCE

Imagine that health care professionals could predict how a patient’s immune system would respond to a treatment before the medicine ever reached the clinic. Envision vaccines with fewer side effects or cancer therapies precisely tailored to each patient’s unique biology.

A collaboration between UNC Charlotte professor of chemistry Kirill Afonin and researchers from the National Cancer Institute and National Center for Advancing Translational Sciences, Marina Dobrovolskaia and Alexey Zakharov, respectively, is bringing this reality closer than ever. Together, they have developed AI-Cell (Artificial Intelligence-Cell) — a first-of-its-kind tool that mimics how human immune cells respond to RNA- and DNA-based nanomedicines. Their innovation has the potential to revolutionize gene therapy, making it safer and more personalized.

“Essentially, AI-Cell is a computational algorithm that thinks like the human immune cell, which will make it possible, ultimately, to better match treatments to patients with certain diseases based on their own biology,” Afonin explained.

This breakthrough addresses a significant challenge in gene therapy: while nucleic acids in medicines and vaccines can boost the body’s natural defenses, they also carry the risk of triggering harmful immune responses. Take, for example, the rapid development of COVID-19 vaccines using mRNA technology. While incredibly effective, these vaccines were tested extensively to ensure they didn’t provoke severe reactions. Similarly, cancer patients undergoing chemotherapy often face debilitating side effects because their immune systems overreact to treatments. AI-Cell offers a way to predict and potentially prevent such issues.

Afonin’s team has joined forces with experts in biology, machine learning and immunology to further diversify and improve the capability of this AI-Cell platform. Prominent among them is UNC Charlotte’s Brittany Johnson, as assistant professor of biological sciences, whose research is designed to gain understanding of pathogen responses to host environments and identify novel therapeutic points of intervention during infection of organs and tissues.

How AI-Cell works

AI-Cell is a digital library of known nucleic acid nanoparticle combinations — and associated immunological responses — freely available to biomedical researchers. With this data, scientists can better predict which compositions, structures, shapes and amounts of nanoparticles will work best to curb disease without causing extremely negative immune responses.

Picture nucleic acid nanoparticles or NANPS, a term coined by Afonin, as Lego blocks. Each NANP is a known structure, yet the options to arrange these blocks into various forms are virtually unlimited.

“If designed correctly, your body will recognize these artificially made NANPs as its own components, which can initiate and guide various biochemical processes and help fix the problem from within,” explained Afonin.

Johnson added, “Often, we think the immune response is always productive. It is a little bit more like a see-saw, and while you want things to be in balance, you need the immune system to peak at a certain time. And then, you want that to resolve, so that the body can go through the healing process.”

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