about

Prime Editing is a next-generation gene editing technology that acts like a DNA word processor, with the power to search and replace genetic sequences at their exact location in the genome, all without making double-strand breaks in DNA.

Prime Editors are designed to produce edits across many tissues, organs and types of cells and to work broadly across most types of gene mutations at the natural genomic location, while minimizing unwanted DNA modifications. This approach uses a process designed to produce a wide variety of precise, predictable and efficient genetic outcomes at the targeted sequence, which we believe will dramatically increase the impact of gene editing for a broad range of therapeutic applications.

science

How Prime Editing Works

Programmable for both search & replace

Exemplary Prime Editing process using Cas and RT. Abbreviations: pegRNA = Prime Editing guide RNA; RT = reverse transcriptase; Cas = CRISPR associated protein

Key Features

  • Programmable and highly flexible
  • High fidelity and specificity
  • High editing efficiency
  • Minimal off-target activity
  • Potential for improved gene function through in situ editing
  • Edits in multiple clinically relevant rapidly dividing, non-dividing, mammalian, non-mammalian cell types and organs
  • No DNA double-strand breaks
  • Validated by multiple independent research laboratories worldwide

versatile

Prime editing can correct all different types of mutations

Point Mutation

Convert any base pair into any other

Point Mutation

Mutated base pairs can be substituted

Insertion Mutation

Extra base pairs can be removed

Deletion Mutation

Missing base pairs can be inserted

Versatile

Prime Editing can make diverse sequence edits at nearly any desired location in the human genome, enabling multiple therapeutic applications. Prime Editors are able to change any base pair to any other base pair to correct all twelve types of single base pair point mutations, delete DNA sequences to correct insertion mutations, or insert DNA sequences to correct deletion mutations. Prime Editors also have the ability to make direct corrections of DNA, correct genetic hotspots, alter the regulatory regions of genes, insert or create premature stop codons, and modify splicing sequences.

precise

one prime editing pegRNA can precisely correct the individual mutations found across many patients

Abbreviations: pegRNA = Prime Editing guide RNA.

Precise

Prime Editing is designed to make only the right edit at the right position within a gene, which greatly minimizes on-target by-products at the site of editing, and results in low, or minimal off-target editing in other places in the genome. Our Prime Editors do not create double-strand DNA breaks, which supports the precision of our technology. Prime Editing requires three “edit checks” or places where there must be a match between the editor and the target DNA in order to complete an edit, which also leads to highly specific and precise edits.

dual flap

dual flap – expanding foundational prime editing technology

Dual Flap Prime Editing

Dual Flap Prime Editing, also known as Twin Prime Editing, uses two Prime Editors working together to make a broader range of edits at a precise location in the genome. The broader range of edits possible with Dual Flap Prime Editing include looping out of large genomic regions such as those occurring in repeat expansion diseases, correcting large hotspot regions in a gene, replacing or removing small exons, or inserting moderate sized sequences. All of these edits occur without double strand breaks, and require the same “edit checks” as in foundational Prime Editing.

efficient

Prime editing corrections occur at the natural place in the genome and are permanent

Efficient

With a single treatment, Prime Editing could create permanent, positive corrections of disease-causing mutations, resulting in restoration of the gene back to its wild-type healthy sequence. A corrected gene would persist in an edited cell, working naturally and being passed along to daughter cells, leading to a potentially durable cure or therapeutic outcome. These benefits have the potential for optimal gene regulation, which we believe could result in long-lasting benefits to patients.

passige

PASSIGE™ – extending Prime Editing to insert gene sized sequences precisely in the genome

Exemplary Prime Editing process using Cas and RT. Abbreviations: pegRNA = Prime Editing guide RNA; RT = reverse transcriptase; Cas = CRISPR associated protein

PASSIGE – Precise introduction of gene-sized pieces of DNA

By combining Prime Editing with an integrase or site-specific recombinase enzyme we harness the precision of Prime Editing with the ability to introduce large gene-sized cargo into the genome as a potential one-time therapy for patients. This proprietary therapeutic approach, known as Prime Assisted Site Specific Integrase Gene Editing or PASSIGE, expands the versatility of Prime Editing, and broadens the range of permanent genomic edits that Prime Editing can make to treat disease, including the ability to insert entire genes precisely into the patient’s genome.

broad

Prime Editing can be delivered to the right place in the body using multiple modalities

Non-viral nanoparticle

RNA-protein complex

Viral vector

Prime-Edited cell therapy

Broad

Prime Editing is a compelling approach for a wide range of therapeutic applications at the genomic level, and can make precise, targeted edits in an array of cell types, tissues and organs. This breadth in applications and ability to target multiple cell types will enable Prime Editing to bring potentially curative gene editing approaches to a broader set of diseases, beyond genetic disease and towards severe, chronic, and acute diseases.