Cian received his PhD in Brain and Cognitive Sciences from MIT in January 2026. In July 2026, he joined the Corn lab as a postdoctoral researcher. His research...
Cian received his PhD in Brain and Cognitive Sciences from MIT in January 2026. In July 2026, he joined the Corn lab as a postdoctoral researcher. His research interests broadly include DNA and RNA tool development and the biology behind editing outcomes.
Genome editing therapies often rely on viral delivery systems such as adeno-associated viruses (AAVs), which have limited cargo capacity. Although RNA-guided...
Genome editing therapies often rely on viral delivery systems such as adeno-associated viruses (AAVs), which have limited cargo capacity. Although RNA-guided nucleases from the Cas12f and TnpB families are attractive alternatives to larger enzymes such as spCas9, their relatively low editing activity in mammalian cells has restricted their broader application till now.
Do you need a super-active CRISPR nuclease for in vivo genome editing? Meet our two new compact editors with SpyCas9-like activity that are small enough for delivery in AAVs.
This exciting work was co-led by Fedor Gorbenko during his PhD and research assistant Iréne Sala, in collaboration with the Schwank lab (UZH) and the Siksnys lab (Vilnius University).
In this study, we developed a directed evolution platform using in a fluorescent reporter system in human cells to engineer compact genome editors with increased HDR efficiency. Through iterative rounds of mutagenesis and screening, we generated Cas12f1Super and TnpBSuper, two enhanced nucleases with up to an 11-fold increase in editing efficiency while maintaining high specificity. Moreover, the resulting variants also exhibit increased NHEJ activity. We further demonstrated efficient in vivo editing of the clinically relevant PCSK9 gene in mice following AAV delivery, with editing efficiencies of up to 61%. These results underscore the potential of Cas12f1Super and TnpBSuper for future therapeutic genome editing applications. When tested as a base-editor, the improved Cas12f1Super variant also substantially boosted the performance, achieving up to a tenfold increase in editing activity compared with the previously developed CasMINI.
By combining compact size with high activity, our Super genome editors broaden the genome engineering toolbox and open new opportunities for both basic research and therapeutic applications.
Congratulations to Fedor, Irene and all collaborators on this exciting achievement!
For more info, check out our new paper in Genome Biology!
A highlight of the summer scientific calendar, the SwissPR Symposium on Genome and Transcriptome Engineering, took place on June 30, 2026, in Basel. Co-organized...
A highlight of the summer scientific calendar, the SwissPR Symposium on Genome and Transcriptome Engineering, took place on June 30, 2026, in Basel. Co-organized by the Corn, Platt, Schwank, Jinek, and Beisel groups, this one-day symposium brought together leading voices from academia and industry to share the latest breakthroughs and real-world applications at the cutting edge of the field.
Congratulations to Charles Yeh, our PostDoc, on a fantastic talk!
From June 8–10, 2026, members of the Corn Lab attended the 14th D-BIOL Symposium in Davos. This biennial ETH Zurich event brought together nearly 500 students,...
From June 8–10, 2026, members of the Corn Lab attended the 14th D-BIOL Symposium in Davos. This biennial ETH Zurich event brought together nearly 500 students, postdoctoral researchers, and faculty members to share the latest scientific discoveries and foster new collaborations across the Department of Biology. Congratulations to Danielle Gallagher and Martina Cernakova for representing the lab with outstanding flash talks!
Miriam received her MSc in Molecular Biology from the University of Vienna in June 2025. During her Master’s thesis in the lab of Dr. Johannes Zuber, she used...
Miriam received her MSc in Molecular Biology from the University of Vienna in June 2025. During her Master’s thesis in the lab of Dr. Johannes Zuber, she used CRISPR-based functional genomics approaches to investigate genetic dependencies in leukemia and solid tumor models. In May 2026, Miriam joined the Corn Lab as a PhD student. Her research interests include functional cancer genomics and epigenomics, DNA damage, and CRISPR technologies.
Camilla Micheli obtained her Bachelor’s degree in Biology from Maastricht University (UM) in 2024. She is currently enrolled in the Microbiology and Immunology...
Camilla Micheli obtained her Bachelor’s degree in Biology from Maastricht University (UM) in 2024. She is currently enrolled in the Microbiology and Immunology Master’s program at ETH Zurich. In the spring of 2025, Camilla carried out a semester project in the Corn Lab, where she assessed the fidelity of base editing sensors in breast epithelial cells. In March 2026, she returned to the lab to begin her Master’s thesis, which focuses on characterising the mechanism of putative oncohistone driver mutations.
Programmable nucleases have transformed genome editing, enabling precise DNA modification for both research and therapeutic applications. However, ...
Programmable nucleases have transformed genome editing, enabling precise DNA modification for both research and therapeutic applications. However, ensuring that these tools cut only at their intended target—and not elsewhere in the genome—remains a key challenge, particularly for clinically relevant platforms where accurate off-target detection is essential.
In our latest collaboration with the Genome Engineering and Measurement Lab (GEML) and Allogene Therapeutics, we introduce DisTAL-Seq, a method that enables genome-wide detection of TALEN-induced DNA double strand breaks directly in human cells. The experimental work was led by research technician Lena Kobel. This approach builds on the principles of DISCOVER-Seq and incorporates analysis logic tailored to TALEN binding architecture, including variable repeat specificity, cleavage offset, and dimerization behavior.
Using DisTAL-Seq, we identified and validated editing sites across different TALEN designs and primary human T-cell donors, providing a systematic view of TALEN specificity in clinically relevant contexts.
These results expand the genome-wide profiling approaches developed at GEML and provide a framework for evaluating the safety and performance of genome editing nucleases as they move towards therapeutic applications.
For more detail, check out our paper in Molecular Therapy: Nucleic Acids.
Stimulation of the innate immune system by foreign RNA triggers a strong interferon response that helps cells defend against infection. However, this powerful...
Stimulation of the innate immune system by foreign RNA triggers a strong interferon response that helps cells defend against infection. However, this powerful defense mechanism can also lead to cell death if not properly controlled. How do cells maintain this delicate balance?
Our latest breakthrough was led by postdoc Eric Aird in collaboration with the Hale Lab (University of Zurich), Recher Lab (University of Basel, University Hospital Basel), Jackson Lab (UCAM) and University of Kuwait.
Using genome-wide CRISPR screens and follow-up cellular biochemistry experiments, we discovered that speckled protein 110 (SP110) functions as a key safeguard against cell death triggered by interferon signaling.
Mechanistically, the study revealed that SP110 interacts with the nuclear body protein SP100 to regulate the disassembly of nuclear promyelocytic leukemia (PML) bodies. Loss of SP110 made cells highly sensitive to interferon stimulation, led to mitotic retention of SP100 and PML bodies, which associated with and perturb segregating chromosomes, leading to micronucleus formation, DNA damage and genotoxic cell death. Conversely, restoring SP110 protected cells from this lethal response. The SP100-SP110 axis is molecularly achieved by newly described functions for the SP100 and SP110 CARD domains that mediate assembly and disassembly of SP100 oligomers. By controlling this process, SP110 helps maintain a balance between effective immune signaling and cell survival.
These findings highlight regulated disassembly of phase-separated biomolecular bodies as essential for cell health and that its failure may contribute to diverse human diseases.
For more details, please visit Nature Cell Biology!
DNA double-strand breaks (DSBs) are among the most dangerous forms of DNA damage, threatening genome stability but also serving as essential intermediates...
DNA double-strand breaks (DSBs) are among the most dangerous forms of DNA damage, threatening genome stability but also serving as essential intermediates for many genome-editing technologies. A key question in the field is how cells repair different types of DSBs and what factors ensure that repair outcomes remain accurate.
In our new study, we uncover an important role for the DNA repair factor ERCC6L2 in safeguarding the repair of staggered DNA breaks, a type of DSB produced by several genome-editing tools. This exciting new work way led by our postdocs Eric Aird and Sebastian Siegner together with Almudena Serrano-Benítez from the Jackson lab (UCAM), together with the Cejka (USI) and Cathomen groups and colleagues from the University of Freiburg and IBSAL.
Using genome-wide CRISPR interference (CRISPRi) screening, we identified ERCC6L2 as a critical factor required for accurate repair of staggered DSBs generated by Cas12, TALENs, or dual Cas9 nicks. Interestingly, ERCC6L2 was not required for repairing the blunt DSBs typically produced by Cas9, revealing that different break structures rely on distinct repair mechanisms.
We found that ERCC6L2 protects staggered DNA ends and prevents harmful repair outcomes such as large deletions and chromosomal translocations. Mechanistically, ERCC6L2 counteracts the activity of the MRN complex (MRE11–RAD50–NBS1), limiting excessive DNA end resection and promoting accurate end joining.
Loss of ERCC6L2 sensitized cells to damage caused by multiple staggered breaks and increased genome instability following genome editing. These findings highlight ERCC6L2 as an important guardian of genome integrity and provide new insight into how cells respond to structurally diverse DNA breaks.
Beyond fundamental DNA repair biology, this work also has practical implications for genome engineering. Because many editing systems create staggered DNA ends, understanding how ERCC6L2 shapes repair outcomes may help improve editing accuracy and guide the safe use of these tools, particularly in therapeutic contexts. Our data reveal a protective role of ERCC6L2 in staggered-end DSB repair, shedding light on the molecular basis of pathology of ERCC6L2 mutations, which in humans most commonly present as inherited bone marrow failure and leukemia. The findings also suggest caution when considering therapeutic genome-editing strategies that rely on nucleases generating DNA overhangs for their treatment.
For more info, check out our new paper in Nature Communications!
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