Tune Therapeutics represents an emerging class of medical treatments designed to precisely manage gene activity. These therapies adjust how genes are expressed, rather than altering the fundamental DNA sequence itself. This approach influences the cellular machinery that controls gene function, aiming to correct cellular dysfunction and disease.
Understanding Epigenetic Control
Epigenetics refers to changes in gene expression that do not alter the underlying DNA sequence. Instead, these changes are driven by “marks” on DNA or associated proteins, influencing whether a gene is turned on or off, or how much protein it produces. These modifications guide cells to perform specific functions and differentiate. For example, a skin cell and a brain cell have the same DNA, but their unique functions arise from different epigenetic instructions.
Two primary mechanisms of epigenetic control are DNA methylation and histone modification. DNA methylation involves adding a methyl group directly to the DNA molecule, typically at specific cytosine bases. This addition can block the machinery that reads genes, effectively silencing them. Histone proteins act as spools around which DNA is wound. Chemical modifications to these histones can either tighten or loosen the DNA’s grip, making genes more or less accessible for expression. These dynamic epigenetic changes are fundamental to normal cellular processes, but their dysregulation can contribute to various diseases.
How Tune Therapeutics Works
Tune Therapeutics employs advanced technologies to precisely manipulate epigenetic marks, adjusting gene activity. The goal is to activate, silence, or fine-tune the output of specific genes to correct cellular imbalances. Their proprietary platform, TEMPO, allows for the up or down regulation of gene expression without making permanent changes or cuts to the DNA sequence.
These therapies often utilize tools derived from CRISPR technology, such as deactivated Cas9 (dCas9) fused with epigenetic modifiers. Unlike traditional CRISPR, which cuts DNA, dCas9 can be guided to specific gene regions without causing breaks. Once at the target, the fused epigenetic modifiers can add, remove, or alter chemical tags on DNA or histones, influencing gene activity. This targeted approach allows for precise control of gene behavior, addressing the root causes of disease.
The delivery of these epigenetic editors to target cells often involves lipid nanoparticle (LNP) technology, a method also utilized in some vaccine developments. This system helps transport the therapeutic agents into cells, ensuring they reach the intended genetic targets. Tune Therapeutics aims to offer a controlled and temporary adjustment of gene function, potentially reversing cellular dysfunction.
Diseases Targeted by Tune Therapeutics
Epigenetic dysregulation contributes to a variety of medical conditions, making them potential targets for Tune Therapeutics. The company is exploring applications across several disease categories where altering gene expression could offer therapeutic benefits. This includes genetic disorders, where epigenetic changes might compensate for underlying genetic mutations or directly address the pathology.
Certain cancers also exhibit significant epigenetic alterations that drive tumor growth, and therapies that can reset these changes are under investigation. Neurological conditions, such as Alzheimer’s and Parkinson’s diseases, are areas of interest, as epigenetic modifications are recognized for their role in brain function and neurodegeneration. Autoimmune diseases, characterized by immune system dysregulation, could also benefit from therapies that fine-tune gene expression to restore immune balance. Tune Therapeutics is specifically testing an epigenetic treatment for chronic Hepatitis B in clinical trials, a condition affecting over 250 million people globally and a leading cause of liver cancer.
Current Developments and Future Directions
Tune Therapeutics is actively advancing its research and development in epigenetic editing. The company launched in 2020 and has been progressing its proprietary TEMPO platform. They have initiated early-stage clinical trials in New Zealand and Hong Kong, focusing on an epigenetic treatment for chronic Hepatitis B.
Pre-clinical studies have demonstrated the technology’s ability to repress specific genes in non-human primates, showing a sustained reduction in LDL cholesterol levels for nearly two years after a single treatment. This suggests the potential for long-lasting effects. The field continues to evolve with advancements in precision targeting and delivery methods for epigenetic therapies. While still in its early stages of development, Tune Therapeutics aims to offer durable or even curative treatments by addressing the fundamental mechanisms of disease at the gene expression level.