I was introduced to antisense in 1986 while I was at MRC, Cambridge, UK, and received a call from Paul Zamecnik, the pioneer of antisense technology. Soon after, I joined his basement labs at the Worcester Foundation for Experimental Biology (now UMass Chan Medical School) in Shrewsbury, MA. Our objective was to provide drug-like properties to antisense sequences. We were at the forefront of the development of antisense; we addressed the issues related to chemistry, mechanisms, delivery, safety, non-clinical and clinical development, and manufacturing. All of this work was carried out in collaboration with talented colleagues and collaborators whose names and association are listed in publications.

In 2017, I took a break to spend time on other interests. During my hikes on local trails, I started to think about key developments in RNA therapeutics and why our thirty-year old inventions, including gapmer chemistry and modified RNA, are still foundational platforms in the space that are widely used in approved drugs and in candidates currently in development. While writing reviews on our work, it became clear that insights were available to connect the dots differently and create better drugs.

This led me to establish Arnay Sciences, where I continue connecting the dots between old and current observations. I refer to this part of my work as the chemical engineering of oligonucleotides. For example, strategic placements of chemical blocks in oligonucleotides, both DNA and RNA, result in a significant increase in potency and specificity. This work has broad applicability in developing RNA therapeutics based on diverse mechanisms.