The Next Generation

Genetic tuning will enable the next generation of gene and cell therapies – shifting the treatment paradigm from a limited range of rare monogenic conditions, to overcoming thousands of diseases that involve the interaction of multiple genes, cell types, and metabolic pathways.

With its unique ability to fine-tune cell properties – combined with the power to direct entire cell states, fates, and phenotypes via multiplex editing – genetic tuning opens the door to the rapid development and application of effective, regenerative therapeutics.

 

The history of genetic medicine

  • 1950 — 2000

    Genesis

    Discovery of DNA structure. Deciphering of the genetic code.
    The birth of genetic engineering and medicine.

    Technical Foundations

    Early development of lentiviral, retroviral, and AAV-based gene transfer. First clinical gene therapy trials in humans (SCID).

    Early efforts at genome and epigenome editing using engineered Zinc Finger (ZF) proteins.

    Initial discovery of the CRISPR system in bacteria.

  • 2000-2010

    Elucidation

    Completion of the Human Genome Project with draft sequence of 92% of the human genome.

    First Genome-Wide Association Studies (GWAS) linking genetic variation to human disease.

    ENCODE and Roadmap Epigenomics initiatives begin, seeking to build a map of functional regulatory elements in humans.

    Derivation of induced pluripotent stem cells (iPSCs).

    Early Successes

    Development of site-specific genome editing in human cell lines using Zinc Finger (ZF) and Transcription Activator-Like Effector (TALE) proteins.

    Pioneering AAV-based gene therapy trials for inherited blindness and haemophilia B. Dramatic clinical trial successes of CAR T cell therapy for CD19+ lymphoid malignancies.

  • 2010-2020

    Technical Breakthroughs

    First use of engineered CRISPR systems for gene editing in human cells.

    Development of high-throughput screening and transcriptional modulation with RNA-guided CRISPR/Cas-derived systems.

    Clinical Breakthroughs

    First clinical trials for iPSC-derived cells to generate human retinal tissue, genome editing of autologous T cells vs HIV, and CRISPR-Cas9 for gene disruption in beta-haemoglobinoapthies

    First in vivo cell therapy for inherited blindness.
    First CAR-T cell therapy for refractory B cell lymphoma.

  • 2020-Present

    Crossing the Threshold

    Precision genetic tuning (epigenome editing) enables the controlled activation and repression of genes and gene networks in the absence of DNA breaks, and without reliance on DNA repair pathways – leveraging the full power of genetic medicine for the treatment of common and complex diseases.

The Critical Difference

Where gene editing cuts or swaps DNA, genetic tuning leaves DNA sequences and naturally-encoded mechanisms of gene regulation intact – reducing disruption and providing more fine-tuned, predictable control within complex gene networks.

And critically, because genetic tuning does not create strand breaks in DNA, it is far better suited to working with multiple genes at once (or multiplexing) when compared to other gene therapy modalities.

Across all technologies that alter DNA sequence, any nicking, cutting, or breaking of DNA is always associated with the risk of making unintended changes to the genome at off-target locations. Attempting to target two or more sites multiplies this risk. In short, the more DNA edits you try to make, the greater the potential for variable and unpredictable results.

By contrast, genetic tuning not only provides exquisite target specificity, it also rules out the possibility of off-target DNA damage and repair responses – because no damage is done, and no repair is necessary.

Armed with this technology, we can confidently target not just single genes, but multiple nodes of control within a complex gene network. This expands the scope of genetic tuning to complex diseases involving the interaction of multiple genes and cell types – which describes the vast majority of common and chronic diseases we face in the modern world.

Power and Potential

With the power to target multiple genes and gene networks at once, genetic tuning opens the door to a powerful new possibility in medicine – the ability to shift cell type, state, and function at will.

This follows from two self-evident biological truths:

  • 1
  • All cells types have the same DNA. It is the differences in their epigenetics, not their basic code, that makes them distinct. With enough understanding and control of the epigenetic mechanisms that differentiate stem cells into mature nerve, muscle, or blood cells, you can theoretically turn any given cell type A into any desired cell type B.

  • 2
  • Almost all complex diseases involve a shift in epigenetic cell state during progression. These epigenetic changes trigger and reinforce pathways of cell exhaustion, loss of function, and cell death. Figure out how to reverse these states, and you hold the potential to reverse pathways of disease – including rare monogenic diseases, common tumor development, degenerative brain diseases, and the tissue-specific effects of aging.

This is what we are so excited about at Tune. We are leveraging the awesome power of epigenomic control to create the next generation of genetic therapies. Through our unique therapeutic modality and platform, we believe we can address both rare and common diseases while unlocking the full power and potential of regenerative medicine.

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