We develop technologies to precisely modify genomes and deliver nucleic acid therapeutics to target cells. Our research combines protein and RNA engineering, directed evolution, and computational design with preclinical studies to advance treatments for genetic diseases and cancer.
Engineering Genome-Editing Technologies
The ability to rewrite DNA opens new opportunities to investigate biological processes and treat disease. We engineer genome-editing systems ranging from base- and prime editors for precise sequence changes to emerging technologies for inserting larger DNA sequences. Our goal is to expand the scope of genome engineering while improving editing efficiency, specificity, and versatility.
We combine structure-guided protein and RNA design with directed evolution, high-throughput screening, and machine learning. These complementary approaches allow us to develop improved editors, characterize their activity across diverse targets, and build predictive tools that help researchers design effective editing strategies.
Evolving Cas9 to recognize new DNA targets. High-throughput phage-assisted continuous evolution (HT-PACE) alters PAM recognition bySpCas9. The protein structure illustrates the molecular interactionsunderlying PAM recognition.
Therapeutic Genome Editing In Vivo
Correcting disease-causing mutations directly within the body could provide lasting benefits for patients with genetic disorders. We develop in vivo genome-editing approaches for metabolic liver diseases and neurological disorders, with a particular focus on base- and prime editing.
Our work connects editor design and delivery with rigorous evaluation in preclinical disease models. We investigate editing efficiency, therapeutic benefit, and safety, including the durability of correction and potential unintended effects. A major focus is the treatment of inherited metabolic diseases, including urea cycle disorders. Together with the University Children’s Hospital Zurich, we aim to advance selected programs toward clinical trials, bringing therapeutic genome editing closer to patients.
Visualizing gene correction in the liver. Spatialdetection of disease-associated (yellow) andcorrected (red) sequences in liver tissue from amodel of citrullinemia type I (CTLN1)
Nucleic Acid Delivery and Immune-Cell Engineering
Engineering immune cells extends the therapeutic potential of genome engineering beyond inherited genetic disorders to common diseases such as cancer. By reprogramming how immune cells recognize and respond to disease, we aim to harness their natural capabilities for targeted therapies.
To engineer these cells directly within the body, we combine lipid nanoparticle (LNP)-based nucleic acid delivery strategies with protein and RNA engineering. Our goal is to deliver therapeutic cargo selectively to immune cells and control its expression, enabling efficient in vivo reprogramming.
A key focus is the in vivo generation of chimeric antigen receptor (CAR) T cells that recognize and attack tumors. Beyond introducing CARs, we seek to equip T cells and CAR T cells with additional functions that enhance their activity, persistence, and ability to overcome the immunosuppressive tumor environment. Together, these approaches aim towards enabling more effective and broadly accessible cancer immunotherapies.
Delivery vehicles for immune-cell engineering. Spleen-tropic lipid nanoparticles (LNPs) functionalized with CD8binders enable RNA delivery to CD8⁺ T cells.
Our research is funded by:
–UZH Research Priority Program (URPP) – ITINERARE
–UZH Research Priority Program (URPP) – Human reproduction reloaded