Chroma Medicine is a genomic medicine company focused on developing a new class of single-course therapeutics. The company pioneers epigenetic editing, a unique approach that harnesses nature’s own mechanisms for gene regulation. This technology aims to precisely control gene expression, offering a programmable way to address various diseases with high specificity.
The Science of Epigenetic Editing
The human body contains an intricate system that dictates how genes are used, much like a master cookbook with countless recipes. While the genome represents the static recipes, the epigenome acts as a dynamic set of notes and instructions written in the margins. These notes tell the cell which recipes to use, how much, and when, without altering the original text of the recipe itself.
Epigenetic marks are chemical modifications that attach to DNA or its associated proteins, like histones. One common mark is DNA methylation, where a methyl group is added to the DNA molecule, often leading to gene silencing. Conversely, other marks, such as certain histone modifications, can open up DNA structures, making genes accessible and thereby turning them “on.” These modifications naturally fluctuate, allowing cells to adapt their gene expression in response to internal and external cues.
Chroma Medicine’s Gene Writing Technology
Chroma Medicine’s platform leverages this natural epigenetic control through what they term “gene writing” or “epigenetic writing.” Their technology employs engineered proteins, known as effectors, which are precisely guided to specific locations on the genome. These effectors are designed to add or remove epigenetic marks, such as methylation patterns, at targeted genes.
One example of their innovative approach is the CHARM (coupled histone tail for autoinhibition release of methyltransferase) technology, exclusively licensed from the Whitehead Institute. This compact epigenetic editing effector domain is designed to recruit and activate endogenous DNA methyltransferases. By doing so, CHARM can durably silence target genes by precisely establishing repressive epigenetic marks.
Distinctions from Other Gene Therapies
Chroma Medicine’s epigenetic editing offers a distinct approach compared to traditional gene editing technologies like CRISPR-Cas9. CRISPR-Cas9 systems operate by creating a double-strand break in the DNA molecule, allowing for the addition, deletion, or modification of genetic material. This process fundamentally alters the DNA sequence itself.
In contrast, epigenetic editing regulates gene activity by modifying the epigenetic marks on DNA, leaving the actual DNA sequence untouched. This “no-cut” mechanism avoids the potential risks associated with DNA breaks, such as unpredictable DNA repair outcomes, unintended off-target mutations, or chromosomal rearrangements. The ability to precisely control gene expression without permanently altering the genome presents a potentially safer and more reversible therapeutic strategy, especially when modulating multiple genes simultaneously.
Potential Therapeutic Applications
Chroma Medicine aims to apply its epigenetic editing technology to address a wide range of serious diseases. This includes certain genetic disorders, various forms of cancer, and immunological conditions.
For instance, the technology can be used to silence a gene that contributes to tumor growth or to activate a gene that provides a protective function within the body. A specific example of their preclinical work includes targeting the PCSK9 gene to reduce cholesterol levels, demonstrating durable cholesterol reduction. The company is also developing CRMA-1001, a liver-targeted epigenetic editor, as a potential functional cure for chronic hepatitis B and hepatitis D, with plans to submit a clinical trial application in 2025.