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SCIENCE

Chroma is pioneering the future of single-dose genomic medicines, harnessing epigenetics to unlock precise, predictable, and durable therapies.

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

Our modular platform enables us to develop medicines that address a wide range of complex diseases, whether they require silencing, activation, or targeting multiple genes at once.

The elegance and simplicity of using nature’s endogenous approach for regulating the genome enables an incredibly efficient, precise, and versatile platform. With this, our epigenetic editors have a fundamental mechanistic advantage by completely eliminating expression of the targeted gene. In contrast, current editing approaches indirectly regulate gene expression by cutting the DNA, activating unpredictable DNA repair pathways and potentially producing immunogenic truncated or mutant proteins. These advantages make Chroma’s epigenetic editors the modality of choice for regulating the genome.

Publications & Presentations
PUBLICATIONS & PRESENTATIONS
ASGCT 2024: Simultaneous Five-gene Epigenetic Editing to Generate TGF-β and Adenosine-resistant Allogeneic CAR T Cells
PUBLICATIONS & PRESENTATIONS
ASGCT 2024: Durable and Specific Silencing of Therapeutically Relevant Genes Using Epigenetic Editors Is Reversible In Vivo
PUBLICATIONS & PRESENTATIONS
Keystone Symposia on Precision Genome Engineering 2024: Therapeutic Development of Epigenetic Editors
PUBLICATIONS & PRESENTATIONS
ASH 2023: Durable Multiplex Epigenetic Editing for Generation of Allogeneic CAR T Without Chromosomal Rearrangements