Healthcare & Life Sciences

The dark genome: Pharma’s next billion-dollar bet in therapeutics

Access our full report to unlock insights into the advancements targeting dark genome and discover why Pharma giants are investing billions in this field.

In one month, dark genome startups have attracted over $1B worth of investments, emphasizing the field’s promise. Dark genome projects aim to discover new therapeutic targets to drastically widen the therapeutic options for patients across the board.

Beyond the Human Genome Project:

The Human Genome Project, completed in 2003, was supposed to give us the full blueprint of life, but instead, it revealed something curious. Only about 1-2% of our genome codes for the proteins are responsible for the heavy lifting in human biology. The rest—an overwhelming 98%—was long dismissed as non-functional and irrelevant to study in the context of human health and disease.

Over the last decade, this notion has been turned on its head. This non-coding DNA, often referred to as the “dark genome,” is not the biological wasteland we once imagined. Instead, these regions seem to play crucial roles in regulating, orchestrating, and fine-tuning the functions of our genes.

Today, the dark genome is proving to be a fertile ground for scientific discovery, holding tantalizing clues that could reshape our understanding of human biology and disease (figure 1).

Figure 1. Startups are driving dark genome breakthroughs by uncovering druggable non-coding regions for novel and repurposed therapies.

Pharma invests heavily in dark genome-related projects:

For pharmaceutical companies, the dark genome represents a largely untapped opportunity for drug discovery and therapeutic intervention. This is echoed by the nearly $2B investment from big pharma (figure 2) into various dark genome drug discovery projects. In September 2024, pharma giants Eli Lilly and Bayer effectively tripled the total investment budget in two separate deals between Lilly and HAYA therapeutics (up to $1B in milestone payments) and a $547M investment deal between Bayer and NextRNA.

Figure 2. Investment surge: Big Pharma’s $1B+ deals signal a major shift towards dark genome innovation.

So what is driving these recent major investments into dark genome drug discovery, and why should pharma/biotech companies be interested in this nascent field in drug discovery?

In our extended report (download for free here), we analyzed the overall technological innovations and the advancement of clinical assets that target the dark genome and highlight areas of opportunity.

In conclusion, we argue that two major factors are causing the uptick in interest and investment in the dark genome:

a. The readiness and culmination of combined technological advancements:

1. Advanced AI-driven data analysis (e.g., generative models) and the availability of bigger datasets help unlock insights buried in the complexities of the dark genome.
2. RNA production platforms, pushed by the mRNA vaccines during the pandemic, allow for the scalable production of human therapeutics.
3. Gene-editing platforms such as CRISPR or alternative molecular techniques can modify dark genome elements to tweak expression levels.

b. Early indicators of preclinical success for several drug candidates that target dark genome elements. This serves as a positive feedback loop for investors and further enables scientific progress leveraging upcoming technological platforms as the ones described above.

Have questions or need guidance on navigating the dark genome landscape? Reach out to us here or email us at solutions@prescouter.com

Maikel Boot

Maikel is one of PreScouter’s Technical Directors. He specializes in Healthcare and more recently, Covid-19. After receiving his MS from the VU University in Amsterdam, Maikel continued working there and obtained his PhD in Medical Microbiology from the VU University Medical Center in Amsterdam. His Postdoctoral training was done in Yale’s department of Microbial Pathogenesis, where he obtained an EMBO Fellowship for his research on Tuberculosis. During his time at Yale, he was the Chair of the Yale Postdoctoral Association. Maikel is currently based in Amsterdam, the Netherlands. Connect with Maikel over email at mboot@prescouter.com or on LinkedIn.