Experts: Daniel Blessing (Haya Therapeutics), Ana Catarina Silva (Haya Therapeutics)
What if medicine has been looking for cures in the wrong place? For decades, research has focused on two percent of our genome – the genes that produce proteins. The other 98 percent? Dismissed as “junk DNA”. But it is here, in the dark genome, that researchers are now finding the levers to treat conditions such as heart and lung diseases, cancer and even obesity. The Swiss company Haya Therapeutics has mapped this region and is using it to develop a new generation of precise, customisable drugs. Knowledge of the dark genome is redefining the future of the pharmaceutical industry.
The human genome consists of three billion building blocks. Known as base pairs, they work in a similar way to Lego blocks in that they can be stacked and cross-connected. This creates the familiar and visually striking double-stranded structure of genetic material. Its total length in each cell of the body is two metres. Only two percent of this – four centimetres – consists of coding genes. That is to say, they are translated into proteins and play a role in the body’s composition, structure and function.
What is the remaining 98% needed for? For a long time, researchers assumed that the remaining 2,940 billion base pairs had no function and were merely useless remnants of evolution. These sequences in the genetic material therefore became known as the “dark genome” and were dismissed as junk DNA.
Only in the early 2000s was there more widespread recognition of the fact that genetic sequences do indeed fulfil a function. They influence when, where and how deeply the instructions for genes are read. Consequently, they play an elementary role in the regulation of cellular processes.
We can think of the genome in the form of DNA as the archive. This is stored safely in the nucleus. A working copy – the messenger RNA – is created to translate this into proteins. The large-scale sequencing projects of the early 2000s also proved the existence of another class of RNA molecules: Long non-coding RNAs (lncRNAs) consisting of 200 to thousands of base pairs. They originate from the dark genome and are not translated into proteins.
It is now known that lncRNAs play a central role and control gene expression at different levels. They are the conductors of the genetic orchestra and determine when and where which genes are read. It is not surprising that lncRNA dysregulation is associated with illnesses such as developmental disorders, neurodegenerative diseases, heart failure and cancer. In terms of therapies, a glimmer of hope is found in the fact that the production of lncRNAs is highly tissue-specific. This makes them possible targets for active substances with the promise of minimal side effects.
This is where the Lausanne-based Swiss company Haya Therapeutics, founded in 2019, comes in. It has developed a comprehensive atlas of the dark genome, the HAYAtlas, and the lncRNAs arising from it. CTO and co-founder Daniel Blessing explains: “This atlas is the key component of our technology platform. It combines data from functional multimodal genomics with proprietary algorithms and machine learning methods.” It is based on data from internal research and development as well as publicly available data. The atlas provides information on the tissues in which specific lncRNAs are expressed, identifies their regulatory functions and links these findings with patient data and thus with disease patterns. The groundwork for therapeutic measures has been laid.
Before founding the company, Samir Ounzain, CEO of Haya Therapeutics, was a researcher at the Centre hospitalier universitaire vaudois (CHUV) in Lausanne, where he discovered hundreds of lncRNAs that have a limited effect on heart tissue. One of them is Wisper. Thanks to the HAYAtlas, it was possible to link this lncRNA to cardiac fibrosis, the pathological proliferation of connective tissue in the heart muscle. This results in heart failure. There is no cure for existing fibrosis.
Haya Therapeutics developed a short piece of RNA that binds specifically to Wisper and blocks its function. Because Wisper is only found in the heart, the specificity of the molecule is high and the expected side effects are correspondingly low. HTX-001, as the molecule is called, is the company’s first drug candidate. The results of extensive experiments in cell culture and in animals are promising, with the overactive cells responsible for cardiac fibrosis shown to have stabilised or even recovered. In May 2025, Haya Therapeutics secured 65 million US dollars in a financing round for the clinical development of HTX-001 and the further expansion of the HAYAtlas-based platform.
What works for Wisper and cardiac fibrosis should also work for other diseases, as long as corresponding lncRNAs can be found thanks to the HAYAtlas. The company has identified promising lncRNA candidates whose concentration is increased in the connective tissue surrounding tumour cells. Here, too, a small piece of RNA can give hope: If it binds to and blocks the identified lncRNAs, data from mouse models shows that fibrosis around the tumour cells is reduced. The result is a decrease in tumour mass and a tumour environment that is more accessible to therapeutic approaches than before treatment.
The vision and successes of the young company have met with a positive response in the pharmaceutical industry. In September 2024, Haya Therapeutics announced a multi-year collaboration with the global pharmaceutical firm Eli Lilly and Company. The aim is to find new lncRNAs for the development of treatments for obesity with the help of the proprietary platform HAYAtlas. The contract has a value of up to 1 billion US dollars, including potential milestone payments and royalties.
According to Samir Ounzain, two company founders have a much broader vision: “Our goal is for the medicine of the future to be programmable, precise, preventive and patient-centred – based on interaction with the dark genome in real time.”
