RyboDyn: Unveiling the dark proteome for a new era in precision medicine
Biotech Blueprint's new series highlighting groundbreaking startups and their visionary founders.
Welcome to Startup Spotlight on Biotech Blueprint!
In this series, I dive into the stories of innovative biotech startups and their visionary founders. Each post explores cutting-edge technologies, the challenges and triumphs of entrepreneurship, and the impacts these companies are making in the biotech industry.
In the heart of San Diego, RyboDyn is emerging as a trailblazer in the field of cancer immunotherapy. The company aims to revolutionize treatment by exploring the “dark proteome,” an expansive and largely uncharted realm of cancer-specific proteins. With over 1,000 novel cancer-specific peptides identified, and with multiple confirmed by secondary analyses, RyboDyn’s innovative technology aims to enhance treatment efficacy while minimizing adverse immune reactions.
New approach to precision medicine
Unlike traditional cancer therapies that primarily target minor mutations in proteins conserved between healthy and cancerous cells, RyboDyn’s strategy focuses on deciphering entire peptides unique to cancer cells. This novel approach is set to establish new benchmarks in precision medicine, offering a more tailored and effective method of fighting cancer.
Dr. Corey Dambacher, co-founder, president, and CTO of RyboDyn, shared insights into the company’s mission. With a rich background in scientific research and a passion for innovation, Corey is leading a team dedicated to developing therapies that could redefine cancer treatment.
Corey’s journey into the world of biotechnology began with research on C. elegans. His fascination with neuromuscular function propelled him into cell and molecular biology at San Diego State University, where he published extensively and won international accolades for his work.
He then did his doctorate at the Scripps Research Institute, where he worked alongside brilliant scientists, refining his expertise in biophysical chemistry and next-generation sequencing technologies. After successful stints at various biotech companies, including one that was sold for $800M, Corey co-founded RyboDyn with a vision to explore uncharted territories in cancer therapeutics.
Dark omics: A goldmine for cancer therapy?
Big pharma companies are increasingly exploring the dark genome, targeting long non-coding RNAs (lncRNAs) to develop novel therapies for various diseases. This August, Bayer and NextRNA Therapeutics partnered to create small molecule therapeutics aimed at lncRNAs in oncology, with a focus on disrupting lncRNA interactions with RNA-binding proteins to drive innovative cancer treatments.
Meanwhile, in early September, HAYA Therapeutics joined forces with Eli Lilly to develop RNA-based therapies for obesity and related metabolic conditions. Leveraging HAYA’s RNA-guided regulatory genome platform, this partnership, valued at up to $1B, aims to discover lncRNA targets that can reprogram disease-driving cell states. By focusing on lncRNAs, once considered “transcriptional noise,” both collaborations reflect the growing recognition of their crucial role in gene regulation and disease, from cancer to obesity.
What exactly are the dark genome, dark transcriptome and dark proteome?
The dark genome, dark transcriptome, and dark proteome represent unexplored or poorly understood regions within the flow of genetic information described by the central dogma of molecular biology. According to the central dogma, DNA is transcribed into RNA, which is then translated into proteins. However, much of the dark genome consists of non-coding DNA-regions that do not directly code for proteins but still play important regulatory roles, such as controlling gene expression.
The dark transcriptome refers to RNA molecules that are either transcribed from these non-coding regions of the dark genome but do not lead to protein production, or that are otherwise mis-read or missed entirely by the most commonly used next generation sequencing (NGS) methods. These include some lncRNAs, many microRNAs, and other protein-encoding as well as non-coding RNAs, which regulate gene expression and influence cellular functions.
Finally, the dark proteome involves proteins that are difficult to study or poorly understood, either due to their disordered nature, low abundance, unknown functions, or could not be identified due to the lack of a known encoding transcript (of the dark transcriptome). As per the central dogma outlined above, the problem is that discovery of new proteins requires that researchers first have access to the sequence of RNA (the transcript) encoding these new proteins. Without well annotated RNA sequences, proteins expressed from the dark transcriptome can be detected in experiments, but they cannot be identified.
By targeting lncRNAs, researchers can develop RNA-based therapies to modulate metabolic pathways, potentially offering more precise treatments for obesity and related metabolic conditions, such as diabetes. Targeting specific lncRNAs may also help reprogram cancer cell states, making lncRNAs attractive targets for cancer therapies, either by silencing oncogenic lncRNAs or activating tumor-suppressing lncRNAs.
Back to RyboDyn’s work that centers on the dark proteome—an area rich with potential yet largely overlooked in traditional research. By utilizing a proprietary method to sequence and characterize an entire class of RNA with high accuracy for the first time, they are able to identify and leverage novel proteins specific to cancer cells with the potential to make first in class therapeutics. This is how RyboDyn aims to create cancer therapies that are not only effective, but also safer than the existing treatment options for patients.
Corey explained that the company’s approach also allows for the creation of cancer vaccines to target peptides that are unique to tumors without affecting healthy cells. Importantly, this increased targeting specificity has the potential to significantly reduce off-target effects commonly associated with conventional antibody and cell-based treatments as well.
Expanding beyond cancer
As RyboDyn prepares to advance its platform into new cancer-specific biologics and other therapeutic areas, Corey envisions applications beyond oncology. The potential for addressing autoimmune diseases and chronic inflammatory conditions is particularly promising, as the majority of the newly discovered peptides at RyboDyn are found in healthy tissues, and may play roles in these disorders. The healthy dark proteome discovered at RyboDyn may also play a role in neurological disorders, muscle and cardiovascular disorders and obesity. For this reason, RyboDyn is currently aligning itself with partners to explore alternative applications for their novel targeting approach.
A vision for transformative therapies
With its pioneering research into the dark proteome and commitment to precision medicine, RyboDyn is set to make significant contributions to the field of cancer treatment. The company is currently focused on raising antibodies against its newly confirmed targets and is exploring antibody-drug conjugates (ADCs) as an attractive modality for its in-house therapeutics pipeline. This innovative targeting approach could enhance drug delivery by ensuring highly-specific targeted delivery of payloads directly to cancer cells.
Corey’s leadership and vision reflect a deep understanding of both scientific innovation and patient care, positioning RyboDyn as a key player in the quest for safer and more effective therapies. As the company continues its journey, it not only aims to transform cancer care but also seeks to expand its impact across various therapeutic landscapes, ultimately improving patient outcomes and advancing the frontiers of biotechnology.
Thanks for reading!
A special thank you to Dr. Corey Dambacher for great conversation and sharing his insights.
If you enjoyed this post, please share it with your network and subscribe to this newsletter to discover other exciting startups and support this effort.
Follow RyboDyn on LinkedIn and stay tuned for more inspiring stories!
DISCLAIMER: This content is for informational purposes only. It should not be taken as legal, tax, investment, financial, or other advice. The views expressed here are my own and do not reflect the opinions of any company or institution.
DISCLOSURE: I have no business relationships with any company mentioned in this article.