Prime Medicine Takes Precise Approach to Gene Editing With “Find and Replace” Technology

Article

The precision gene editing technology is designed to minimize off-target genetic alterations.

A new gene therapy-focused company, Prime Medicine, has launched with the goal of using “search and replace” gene editing to provide long-lasting cures to serious diseases.1

The company launched with $315 million in financing, which will be used to continue building the company, rapidly advancing towards clinical indications, and expanding the capabilities of the platform. It expects to employ more than 100 people full-time by the end of 2021.

"Prime Editing is a wonderful example of the revolution in genetic medicine that we are living through," said Robert Nelsen, co-founder and managing director, ARCH Venture Partners, in a statement. "When mature, gene editing technologies like this could totally change our conception of what's possible in treating disease."

"This is an opportunity to take a giant step toward cures for a much wider range of diseases than previously possible," added Stephen Knight, MD, president and managing partner, F-Prime Capital.

Prime Editing gene therapy technology is designed to identify and replace disease-causing genetic sequences at their precise location in the genome without causing double-strand DNA breaks or off-target DNA changes. Prime Medicine believes that the technology has the potential to address over 90% of known disease-causing mutations. It has been shown to work in both dividing and non-dividing human and animal cells.

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Previous research has shown Prime Editing to be able to make precise genome edits with minimal or no off-target editing. The company believes these features overcome technical barriers of earlier gene editing technologies.

"Prime Editing represents an opportunity to do what no gene editing approach has yet been capable of – correcting nearly all types of pathogenic gene mutations, correcting multiple mutations at once, and bringing durable cures to patients across multiple disease areas, potentially with a single 'once and done' treatment approach," said David Schenkein, MD, General Partner, GV, in the statement. "We are tremendously excited about the potential of this technology, and about the talented team at Prime working to bring it to patients."

Previous research with the technology was published in 2019, showing that Prime Editing was supported in 4 human cell lines and primary post-mitotic mouse cortical neurons with varying efficiencies.2 The technology showed higher or similar efficiency and fewer byproducts than homology-directed repair, complementary strengths and weaknesses compared to base editing, and much lower off-target editing than Cas9 nuclease at known Cas9 off-target sites. Since then, Prime Editing has been validated in further research and peer-reviewed articles.1

Prime Editing consists of a prime editor protein with a Cas nickase domain, a reverse transcriptase domain, and a prime editing guide RNA (pegRNA) that carries both a targeting sequence and a template for a replacement sequence. The prime editor finds the target DNA sequence, then uses the pegRNA's "replace" sequence to activate the reverse transcriptase domain to create a corrected DNA sequence from the pegRNA template. The corrected sequence preferentially replaces the original DNA, resulting in a permanent change of the targeted DNA.

"Prime Editing is a transformative technology that we believe will make a significant impact by addressing the fundamental causes of genetic disease," added Keith Gottesdiener, MD, chief executive officer, Prime Medicine. "Since Prime began operations in the summer of 2020, we have continued to make great progress in advancing the performance of Prime Editing, which allowed us to close our Series B financing nine months later. We are operating from a position of financial strength and look forward to further developing the technology and progressing our preclinical programs toward the clinic, with the hope that they may cure or halt the progression of genetic diseases for patients."

REFERENCES
1. Prime Medicine launches with $315 million financing to deliver on the promise of prime editing. News release. Prime Medicine. July 13, 2021. https://www.prnewswire.com/news-releases/prime-medicine-launches-with-315-million-financing-to-deliver-on-the-promise-of-prime-editing-301332085.html
2. Anzalone AV, Randolph PB, Davis JR, et al. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature. 2019 Dec; 576(7785):149–157. doi:10.1038/s41586-019-1711-4
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