Data presented at Mitochondrial Medicine Therapeutic Development (MMTD) annual conference demonstrated ARCUS’ ability to efficiently eliminate mutant mitochondrial DNA without nuclear off-target editing

PBGENE-PMM shifted heteroplasmy by eliminating mutant m.3243 mitochondrial DNA (mtDNA) while repopulating wild type mtDNA, leading to improved mitochondrial function in cells

Precision expects to submit a CTA and/or IND for PBGENE-PMM in 2025

DURHAM, NC, USA I March 19, 2024 I Precision BioSciences, Inc. (Nasdaq: DTIL), an advanced gene editing company utilizing its novel proprietary ARCUS® platform to develop in vivo gene editing therapies for sophisticated gene edits, including gene elimination, insertion, and excision, today announced a poster presentation highlighting new data for the Company’s PBGENE-PMM program, evaluating an ARCUS nuclease as a potential treatment for m.3243-associated primary mitochondrial myopathy (PMM). These data are being presented at the Mitochondrial Medicine – Therapeutic Development Annual Conference, being held from March 18-20, 2024 in Hinxton, UK.

“Today’s data from our PBGENE-PMM program further validate our work with ARCUS and continue to demonstrate its ability to make precise edits while avoiding off-target activity,” said Jeff Smith, PhD, Chief Research Officer of Precision BioSciences. “We believe ARCUS is uniquely suited for editing mitochondrial DNA due to its ability to discriminate a single nucleotide difference, making it ideal for editing point mutations such as m.3243. PBGENE-PMM is designed to eliminate mutant mitochondrial DNA leaving normal functioning wild-type mitochondrial DNA intact to repopulate the cell, resulting in a shift in heteroplasmy and improvement in mitochondrial function.”

Smith continued, “Additionally, ARCUS can cross mitochondrial membranes in order to access the mitochondrial DNA. This is possible because ARCUS is a protein-only editor with both recognition and catalytic activity all in one single protein that does not require a guide-RNA. This is not possible for CRISPR-derived editors such as CRISPR-Cas, Base and Prime editors. We look forward to advancing PBGENE-PMM towards clinical readiness this year and anticipate filing a CTA and/or IND submission in 2025.”

Details for the presentation are as follows:

Title: Shifting m.3243A>G heteroplasmy with PBGENE-PMM: Gene editing therapy for primary mitochondrial myopathy
Poster: P22
Presenter: Wendy Shoop, PhD, Research Lead, Precision Biosciences
Date and Time: Tuesday, March 19, 2024, 6:00-7:00 PM GMT
Location: Hinxton Hall Conference Centre, Wellcome Genome Campus, U.K.

In preclinical work presented today, ARCUS demonstrated highly selective elimination of mutant m.3423G mtDNA. PBGENE-PMM, which contains both a mitochondrial targeting sequence and a nuclear export signal, was found to localize exclusively to mitochondria and without any detectable off-target editing in the nuclear genome. As the m.3243A>G mutation only differs from the wild-type sequence by a single nucleotide, PBGENE-PMM was optimized to prevent cutting of wild-type mtDNA while maintaining activity against mutant mtDNA. When evaluated in cells that contain heteroplasmic m.3243A>G mtDNA, PBGENE-PMM-treated cells were found to contain 0.3% mutant mtDNA three days post-transfection, compared to control cells which contained 95% mutant mtDNA. This robust shift in heteroplasmy resulted in a nearly two-fold increase in both basal and maximal respiration. Together, these data support the development of PBGENE-PMM as a single-treatment, in vivo gene editing therapeutic for m.3243-associated primary mitochondrial myopathy.


PBGENE-PMM is our wholly-owned, first of its kind treatment for m.3243 associated primary mitochondrial myopathy (PMM). Mitochondrial diseases are the most common hereditary metabolic disorder, affecting 1 in 4,300 people. PMM currently lacks a curative treatment and impacts approximately 50% of patients with mitochondrial disease. In the Company’s 2023 publication in Nature Metabolism, Precision presented new data highlighting the high specificity and single component nature of the PBGENE-PMM and ability to specifically edit and eliminate mutant mitochondrial DNA while allowing wild-type (normal) mitochondrial DNA to repopulate in the mitochondria, thus restoring normal function. Precision expects to submit a CTA and/or IND for this program in 2025.


ARCUS is a proprietary genome editing technology discovered and developed by scientists at Precision BioSciences. It uses sequence-specific DNA-cutting enzymes, or nucleases, that are designed to either insert (knock-in), excise (knock-out), eliminate, or repair DNA of living cells and organisms. ARCUS is based on a naturally occurring genome editing enzyme, I-CreI, that evolved in the algae Chlamydomonas reinhardtii to make highly specific cuts in cellular DNA and stimulate gene insertion at the cut site by homologous recombination. Precision’s platform and products are protected by a comprehensive portfolio including more than 130 patents to date.

About Precision BioSciences, Inc.

Precision BioSciences, Inc. is an advanced gene editing company dedicated to improving life (DTIL) with its novel and proprietary ARCUS® genome editing platform that differs from other technologies in the way it cuts, its smaller size, and its simpler structure. ARCUS is a highly precise and versatile genome editing platform that was designed with therapeutic safety, delivery, and control in mind. Using ARCUS, the Company’s pipeline is comprised of in vivo gene editing candidates designed to deliver lasting cures for the broadest range of genetic and infectious diseases where no adequate treatments exist. For more information about Precision BioSciences, please visit

SOURCE: Precision BioSciences