A new technology called D&D-seq allows scientists to map where regulatory proteins bind to DNA within single cells, solving a decades-old technical challenge that has held back fundamental research in genetics and disease biology. The method, developed by researchers at Weill Cornell Medicine and the New York Genome Center, was published in Cell on June 4, 2026, and represents what experts are calling a foundational advance in molecular biology tools.

What Makes This Method Different From Existing Tools?

For years, biologists have struggled to map transcription factors and other regulatory proteins that control which genes turn "on" or "off" in cells. The existing methods had significant blind spots: they missed weak or temporary binding events, and they couldn't easily work alongside other standard research tools that examine multiple layers of cellular information simultaneously.

D&D-seq solves these problems through an elegant approach. The method uses antibodies to position a DNA-editing enzyme called a deaminase close to a target protein. When that protein binds to DNA, even briefly, the deaminase leaves a chemical mark that researchers can later detect through sequencing. Think of it as using DNA itself as a recording device for protein interactions.

"DNA is a marvelous molecule for recording and storing information, and we are exploiting this property to our advantage," said Ivan Raimondi, senior molecular biologist and research innovation director in the Landau Lab.

Ivan Raimondi, Senior Molecular Biologist, Weill Cornell Medicine

The researchers demonstrated D&D-seq's capabilities by mapping the binding sites of several transcription factors and chromatin remodeling proteins, which are proteins that influence gene activity by opening or closing the twisted structure of DNA. In one particularly striking demonstration, they mapped how a common leukemia mutation changes where a key transcription factor binds in blood cells, revealing the molecular consequences of the mutation in detail.

Why Should Researchers and Patients Care About This Breakthrough?

The implications extend far beyond basic research. A large proportion of disease-risk hotspots identified in genetics studies are located at transcription factor binding sites, meaning understanding these proteins is crucial for understanding disease. Additionally, transcription factors are increasingly becoming targets for new therapies, making tools to study them essential for drug development.

What sets D&D-seq apart is its compatibility with existing research platforms. The method is what researchers call "platform-agnostic," meaning it works as a plug-and-play addition to standard single-cell multi-omics workflows. Multi-omics refers to analyzing multiple layers of cellular information simultaneously, including DNA sequences, gene activity patterns, and protein populations.

"D&D-seq is platform-agnostic, it's basically a plug-and-play feature that you can add to existing platforms to get more information from your experiments," explained Ivan Raimondi.

Ivan Raimondi, Senior Molecular Biologist, Weill Cornell Medicine

How Researchers Can Adopt and Use D&D-seq

• Integration with existing platforms: D&D-seq can be added to standard single-cell multi-omics platforms without requiring researchers to overhaul their current workflows or equipment.
• Training and adoption: The research team is already training scientists from other laboratories in how to use the method, with plans to make it widely available across the research community.
• Commercialization pathway: The developers aim to commercialize D&D-seq, which would make the technology accessible to academic and industry research groups worldwide.

Dr. Dan Landau, the Bibliowicz Family Professor of Medicine at Weill Cornell and co-senior author of the study, emphasized the transformative potential of this work. "A lot of research has been held back because we didn't have the right tools for mapping DNA-protein interactions in single cells; and now that we have such a tool there is enormous excitement, it's really a foundational technological advance," Landau stated.

"We're entering an era of medicine in which transcription factors and other gene-activity regulators will increasingly be therapeutic targets. This kind of technology should have an important role in developing and evaluating such therapies," said Dr. Dan Landau.

Dr. Dan Landau, Bibliowicz Family Professor of Medicine, Weill Cornell Medicine

The research team acknowledges that D&D-seq is still a work in progress, with many improvements planned for future versions. However, the current version already demonstrates sufficient capability to be useful for multi-omics research, allowing scientists to map DNA-protein interactions alongside related measurements of gene activity patterns, overall genome sequences, and other cellular information layers in individual cells.

The study was led by Wei-Yu Chi, a doctoral candidate in the Weill Cornell Graduate School of Medical Sciences, and Sang-Ho Yoon, a postdoctoral associate in medicine in the Landau lab, alongside the two senior authors. A patent application has been filed for the technology, and the research team has disclosed intellectual property related to this work.

As this technology becomes more widely adopted, it could accelerate research across multiple fields, from understanding how mutations drive cancer to developing new approaches for treating genetic diseases and improving precision medicine more broadly.