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SCIENCE

Chroma is harnessing epigenetics to deliver highly potent, durable, and specific therapies to patients with serious diseases.

The epigenome is nature’s gatekeeper of gene expression

Epigenetics is the endogenous cellular system that determines the identity and function of each cell by controlling expression patterns of all genes. Although every cell in an individual has the same genome, each has a vastly different morphology, function, and phenotype. This is possible because each cell type has a unique and durable gene expression pattern which is established and maintained by epigenetics. This elegant system regulates which genes are expressed without altering the DNA sequence by laying down epigenetic marks such as methyl groups on the DNA, making genes accessible or inaccessible for transcription.

Programmable editors for precise control

Chroma’s novel programmable epigenetic editors couple a DNA binding domain with a modular epigenetic effector domain to target genes and control chromatin conformation. The DNA binding domain specifically targets the gene (or genes) to be silenced or activated. The effector domains create specific and durable methylation patterns which control chromatic conformation and govern whether a gene is accessible or inaccessible for transcription. This efficiently and effectively mimics the cell’s innate mechanisms for controlling gene expression.

A modular platform for epigenetic editing

Using nature’s endogenous approach for regulating the genome enables an incredibly efficient, precise, and versatile platform. Our epigenetic editors have a fundamental mechanistic advantage by silencing or activating the targeted gene without cutting or nicking the DNA. This is in contrast with how current editing approaches indirectly regulate gene expression. By cutting or nicking the DNA, those editing approaches can activate unpredictable DNA repair pathways and potentially produce immunogenic truncated or mutant proteins. These advantages make Chroma’s epigenetic editors the future of gene regulation.

Publications & Presentations
PUBLICATIONS & PRESENTATIONS
Chroma HBV 2024: Pre-clinical development of CRMA-1001, an epigenetic editor for the treatment of chronic hepatitis B
PUBLICATIONS & PRESENTATIONS
ESC 2024: Epigenetic Editor Targeting Human PCSK9 Efficiently and Durably Lowers LDL-C in NHPs
SUPPORTING LITERATURE
Neumann EN, Bertozzi TM, Wu E, et al. Brainwide silencing of prion protein by AAV-mediated delivery of an engineered compact epigenetic editor. Science. 2024.
PUBLICATIONS & PRESENTATIONS
Chroma FASEB 2024 Epigenetic Editing to Treat Human Disease