Leveraging Synthetic DNA to Address Immune Enzymes Gone Awry
The APOBEC3 family of enzymes form part of our immune system and help protect us from DNA-based viruses by mutating their genetic code. However, these same enzymes can sometimes “misbehave” and lead to drug resistance, such as in HIV patients. They can also begin to mutate our own DNA, leading to cancers including lung, cervical, bladder, and head and neck cancer. Currently, no drugs exist for inactivating APOBEC3 enzymes gone awry, despite attempts using traditional inhibitor design methods. My research focuses on developing APOBEC3 inhibitors using a new approach. I plan to make short pieces of synthetic DNA, termed oligonucleotides, that mimic the preferred DNA targets of APOBEC3 enzymes. These oligonucleotide inhibitors will be specifically designed and tailored to each APOBEC3 enzyme. Ultimately, this work will allow us to better study and understand these enzymes, and hopefully help to design a new class of drugs for the clinic.
It’s an honor to be awarded a predoctoral fellowship from the PhRMA Foundation. With their support, I am excited to continue innovative Drug Discovery merging structure-based drug-design with oligonucleotide chemistry.