General Control is building epigenetic editing therapies to upregulate or downregulate any gene in a human genome, to any level, durability, and at any combination. We believe these synthetic transcription factors would be one of the biggest progress-multipliers in our ability to treat aging and multifactorial disease.
Our North Star is programmable therapies that can rewrite the expression of multiple genes at once. Diseases like Alzheimer’s or sarcopenia contain many interacting phenotypes, and the paradigm of “one molecule targeting one protein” is yet to slow their progression, let alone reverse it. Combination therapies are usually explored only after each component has separately completed its development pipeline, often decades later, selecting against mechanisms that are weak in isolation but synergistic together. Multiplexed epigenetic editors change this by enabling coordinated, locus-specific control of several nodes in a disease network within a single therapy.
GENERAL CONTROL VISION
GENERAL CONTROL VISION
The epigenome stores many of the programs that cells run – cell type, cell’s developmental stage; it integrates its intrinsic and environmental cues to maintain lineage, run state transitions, and activate or repress networks that counteract disease. In GWAS, ~90% of disease-linked variants change gene regulation, not the protein itself. We have decades of evidence implicating epigenetic states in the process of aging.
This recognition set off decades of attempts to influence epigenetic programs – HDAC inhibitors, reprogramming through environmental control or transcription factors, as well as the first work to rewrite the epigenome at a single-gene level. However, today, the safety, precision, and genome-wide scalability gap between epigenetic tools and epigenetic therapies is yet to be closed. We believe epigenetic editors can enable medicines that make precise, lasting adjustments to gene expression while preserving cellular identity.
This recognition set off decades of attempts to influence epigenetic programs – HDAC inhibitors, reprogramming through environmental control or transcription factors, as well as the first work to rewrite the epigenome at a single-gene level. However, today, the safety, precision, and genome-wide scalability gap between epigenetic tools and epigenetic therapies is yet to be closed. We believe epigenetic editors can enable medicines that make precise, lasting adjustments to gene expression while preserving cellular identity.
As a company developing a novel therapeutic modality, we are standing on the shoulders of Giants – and aspire to learn from them. Taking antibodies, CAR-Ts, siRNA / ASO oligonucleotides, and mRNA therapeutics from little-known papers to consensus medicines required early wins that validated the technology, while also unambiguously demonstrating its counterfactual impact. We view this as the modality’s right-to-exist; it is not sufficient for a new modality to be new – it has to solve a big gap in medicine.
For this reason, our first screening focus was on gene activation. Most drugs are created as suppressors – of all approved small molecules, 88% inhibit, block, or degrade a protein. Durable and safe upregulation has not been broadly available, and activation tooling in epigenetic editing has historically lagged. We began by building miniature epigenetic activators that stably upregulate genes at their native loci, outperforming recombinant protein benchmarks, and offering a safety and tunability profile not possible with AAV-based gene therapies. This makes previously intractable targets – those limited by short half-life, isoform complexity, or dependence on multiple post-translational modifications – accessible in a way they have not been before.
A parallel gap exists for silencing. RNAi and ASOs showed that pathogenic proteins can be suppressed, but only through chronic dosing. For multifactorial disease, chronic means decades of injections across multiple targets, with adherence risk, cumulative exposure, clinic time, drug–drug interactions, and rising total cost of care. Chromatin-level silencing allows us to replace chronic maintenance with one-time correction, reducing the lifetime burden associated with managing comorbidities.
Biology’s biggest leaps have come from tools that created a step change in capability: recombinant DNA made it possible to engineer genes, PCR made it possible to amplify them in hours, and high-throughput sequencing made it possible to read them at scale. Each turned previously inconceivable experiments into routine workflows, multiplying the pace of discovery. As Sydney Brenner famously said, “Progress in science depends on new techniques, new discoveries, and new ideas, probably in that order.”
With this, we believe that new therapeutic modalities will be the biggest multipliers in our ability to treat diseases of aging. Our long-term mandate is to create for patients a world where we can rewrite cell states, precisely and at will, to systematically take away the limits that linear progress on aging and disease has placed on us.
For this reason, our first screening focus was on gene activation. Most drugs are created as suppressors – of all approved small molecules, 88% inhibit, block, or degrade a protein. Durable and safe upregulation has not been broadly available, and activation tooling in epigenetic editing has historically lagged. We began by building miniature epigenetic activators that stably upregulate genes at their native loci, outperforming recombinant protein benchmarks, and offering a safety and tunability profile not possible with AAV-based gene therapies. This makes previously intractable targets – those limited by short half-life, isoform complexity, or dependence on multiple post-translational modifications – accessible in a way they have not been before.
A parallel gap exists for silencing. RNAi and ASOs showed that pathogenic proteins can be suppressed, but only through chronic dosing. For multifactorial disease, chronic means decades of injections across multiple targets, with adherence risk, cumulative exposure, clinic time, drug–drug interactions, and rising total cost of care. Chromatin-level silencing allows us to replace chronic maintenance with one-time correction, reducing the lifetime burden associated with managing comorbidities.
Biology’s biggest leaps have come from tools that created a step change in capability: recombinant DNA made it possible to engineer genes, PCR made it possible to amplify them in hours, and high-throughput sequencing made it possible to read them at scale. Each turned previously inconceivable experiments into routine workflows, multiplying the pace of discovery. As Sydney Brenner famously said, “Progress in science depends on new techniques, new discoveries, and new ideas, probably in that order.”
With this, we believe that new therapeutic modalities will be the biggest multipliers in our ability to treat diseases of aging. Our long-term mandate is to create for patients a world where we can rewrite cell states, precisely and at will, to systematically take away the limits that linear progress on aging and disease has placed on us.
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