By Erin Harris, Editor-In-Chief, Cell & Gene
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ARM’s April 2023 Sector Snapshot states gene editing as having entered the mainstream. For example, CRISPR Therapeutics and Vertex Pharmaceuticals are anticipated to receive the first ever U.S.-marketed treatment based on CRISPR this year for their Exa-cel therapeutic. ARM also briefly mentions prime editing, base editing, and epigenetic editing as the next generation approaches to gene editing. For this article, I dug a bit deeper into prime editing, a technique that can alter longer lengths of DNA. I caught up with Ann L. Lee, Ph.D., Chief Technical Officer at Prime Medicine, a biotech created to deliver on the promise of prime editing, to learn more about prime editing’s potential to make wholesale changes to DNA at one time. Here’s what she had to say.
Explain Prime Medicine.
Prime Medicine is a biotechnology company created to deliver on the promise of Prime Editing, a breakthrough gene editing approach that could potentially be used to transform the lives of patients by addressing the genetic cause of their disease. Prime Editing (described below) was invented at the Broad Institute in the laboratory of David Liu, one of our scientific founders. Prime Medicine has assembled an experienced team of drug developers and scientific innovators who together are translating Prime Editing technology into therapeutics in multiple disease areas, including diseases of the blood, liver, eye, ear, muscle, lung, central nervous system, and beyond.
What is prime editing?
Prime Editing is a gene editing technology that acts like a DNA word processor to precisely correct disease-causing mutations, or otherwise modify genes to achieve a desired therapeutic effect. A powerful feature of Prime Editing is the versatility offered by its “search-and-replace” mechanism. By applying simple design rules, a Prime Editing system can be programmed to search for a specific DNA sequence, then replace the targeted DNA sequence with a new sequence—for example, a disease-causing DNA sequence can be targeted and replaced with a healthy DNA sequence. The Prime Editing mechanism enables multiple types of DNA changes, including all types of single DNA base substitutions (e.g., C to A, or G to C), precise sequence insertions, precise sequence deletions, and combinations thereof. Together, these classes of gene edits could in principle address approximately 90% of known disease-causing variants. Prime Editing technology also has capabilities to carry out larger DNA sequence edits, including the removal of large DNA repeat sequences such as those that occur in Huntington’s disease, as well as targeted integration of gene-sized pieces of DNA using an approach that we call PASSIGETM.
Importantly, Prime Editing does not create double-strand DNA breaks. As a result, Prime Editing precisely incorporates the desired edit at the targeted DNA site with minimal to no detectable off-target editing activity at other locations in the genome, which we believe could have important safety implications. Lastly, Prime Editing efficiently corrects mutations in many different cell types and tissues that are relevant for human therapeutic applications, and the corrective edits that it introduces are passed on to daughter cells, potentially making the benefits of those edits very durable.
How is it impacting unmet need?
Our Prime Editing technology has the potential to correct approximately 90% of the genetic variants associated with human disease. As a result, Prime Editing could be applied to numerous therapeutic indications, many of which have few effective treatment options and high unmet medical need. Prime Medicine has built a pipeline that reflects the broad potential applicability of Prime Editing to address diseases that are otherwise challenging to treat. Over time, we intend to maximize Prime Editing’s therapeutic potential and advance potentially curative therapeutic options to patients for a broad spectrum of diseases. We believe Prime Editing can address the genetic cause of a disease and it offers the potential of a one-time treatment that is both precise and durable, meaning that the benefit to patients could be long-lasting.
What is Prime Medicine focused on throughout the remainder of 2023?
In 2023, we are focused on advancing our pipeline and moving our Chronic Granulomatous Disease program toward the clinic by initiating IND-enabling studies. We also intend to continue developing our platform technology, including our PASSIGE approach for targeted gene integration, as well as delivery systems for our therapeutic programs. We hope to further demonstrate superior off-target profiles for Prime Editing systems and expand our preclinical proofs-of-concept with in vivo studies.