2024 ANNUAL REPORT

| 64 | 2024 Annual Report Anti Leishmania Live imaging of bursting the lysosome upon treatment of T. brucei cells with conPEI25CAN-Ɣ-Fe2O3 NPs. Prof. Levanon Erez The Mina & Everard Goodman Faculty of Life Sciences Genome Plasticity Research Areas • Structural and computational biology Abstract We study the dynamics of genetic information and how it affects disease, evolution and behavior. Specifically, we develop technology and algorithms to uncover the full extent of A- to-I RNA editing in human and animal models. We are also developing technology to manipulate the genomic information by recruiting endogenous cellular RNA editing processes. Pre-mRNA molecules transcribed from the genome may fold to form double-stranded RNA structures. ADAR enzymes bind these structures and deaminate some adenosines to inosines. If these inosines are located in an exon, they will be present in the mature mRNA. Publications 2023 and 2024 • Philipp Reautschnig, Carolin Fruhner, Nicolai Wahn, Charlotte P Wiegand, Sabrina Kragness, John F Yung, Daniel T Hofacker, Jenna Fisk, Michelle Eidelman, Nils Waffenschmidt, Maximilian Feige, Laura S Pfeiffer, Annika E Schulz, Yvonne Füll, Erez Y Levanon, Gail Mandel, Thorsten Stafforst. “Precise In Vivo RNA Base Editing with a Wobble-Enhanced Circular CLUSTER Guide RNA.” Nature Biotechnology, 2024. • Chunhua Dai, Ajay K Singh, Rebekah Brantley, Amber Bradley, Regina Jenkins, Diane C Saunders, Marcela Brissova, Erez Y Levanon, Agnes Klochendler, Yuval Dor, Aalvin C Powers. “349-OR: Reduction of RNA-Editing Enzyme ADAR1 in Human Islets Triggers an Interferon Response and Impairs Beta-Cell Function.” Diabetes, 2024. • Nina Schneider, Ricky Steinberg, Amit Ben-David, Johanna Valensi, Galit David-Kadoch, Zohar Rosenwasser, Eyal Banin, Erez Y Levanon, Dror Sharon, Shay Ben-Aroya. “A Pipeline for Identifying Guide RNA Sequences that Promote RNA Editing of Nonsense Mutations that Cause Inherited Retinal Diseases.” Molecular Therapy-Nucleic Acids, 2024. • Ariel Dadush, Rona Merdler-Rabinowicz, David Gorelik, Ariel Feiglin, Ilana Buchumenski, Lipika R Pal, Shay BenAroya, Eytan Ruppin, Erez Y Levanon. “DNA and RNA Base Editors Can Correct the Majority of Pathogenic Single Nucleotide Variants.” npj Genomic Medicine, 2024. • Udi Ehud Knebel, Shani Peleg, Chunhua Dai, Roni Cohen-Fultheim, Sara Jonsson, Karin Poznyak, Maya Israeli, Liza Zamashanski, Benjamin Glaser, Erez Y Levanon, Alvin C Powers, Agnes Klochendler, Yuval Dor. “Disrupted RNA Editing in Beta Cells Mimics Early-Stage Type 1 Diabetes.” Cell Metabolism, 2024. • Erez Y Levanon, Roni Cohen-Fultheim, Eli Eisenberg. “In Search of Critical dsRNA Targets of ADAR1.” Trends in Genetics, 2023. • Rona Merdler-Rabinowicz, David Gorelik, Jiwoon Park, Cem Meydan, Jonathan Foox, Miriam Karmon, Hillel S Roth, Roni Cohen-Fultheim, Galit ShohatOphir, Eli Eisenberg, Eytan Ruppin, Christopher E Mason, Erez Y Levanon. “Elevated A-to-I RNA Editing in COVID-19 Infected Individuals.” NAR Genomics and Bioinformatics, 2023. • Marlon S Zambrano-Mila, Monika Witzenberger, Zohar Rosenwasser, Anna Uzonyi, Ronit Nir, Shay Ben-Aroya, Erez Y Levanon, Schraga Schwartz. “Dissecting the Basis for Differential Substrate Specificity of ADAR1 and ADAR2.” Nature Communications, 2023. • Miriam Karmon, Eli Kopel, Aviv Barzilai, Polina Geva, Eli Eisenberg, Erez Y Levanon, Shoshana Greenberger. “Altered RNA Editing in Atopic Dermatitis Highlights the Role of Double-Stranded RNA for Immune Surveillance.” Journal of Investigative Dermatology, 2023. • Gwendoline Astre, Tehila Atlan, Uri Goshtchevsky, Adi Oron-Gottesman, Margarita Smirnov, Kobi Shapira, Ariel Velan, Joris Deelen, Tomer Levy, Erez Y Levanon, Itamar Harel. “Genetic Perturbation of AMP Biosynthesis Extends Lifespan and Restores Metabolic Health in a Naturally Short-Lived Vertebrate.” Developmental Cell , 2023. • Dror Sharon, Nina Schneider, Johanna Valensi, Ricky Steinberg, Amit Eylon, Eyal Banin, Erez Y Levanon, Shay Ben-Aroya. “RNA Editing of Mutations Causing Inherited Retinal Diseases Using the Cellular Deaminase Acting on RNA (ADAR) Enzyme.” Investigative Ophthalmology & Visual Science, 2023. • Tomer D Mann, Eli Kopel, Eli Eisenberg, Erez Y Levanon. ”Increased A-to-I RNA Editing in Atherosclerosis and Cardiomyopathies.” PLOS Computational Biology, 2023. • Amina Jbara, Kuan-Ting Lin, Chani Stossel, Zahava Siegfried, Haya Shqerat, Adi Amar-Schwartz, Ela Elyada, Maxim Mogilevsky, Maria Raitses-Gurevich, Jared L Johnson, Tomer M Yaron, Ofek Ovadia, Gun Ho Jang, Miri Danan-Gotthold, Lewis C Cantley, Erez Y Levanon, Steven Gallinger, Adrian R Krainer, Talia Golan, Rotem Karni. “RBFOX2 Modulates a Metastatic Signature of Alternative Splicing in Pancreatic Cancer.” Nature, 2023. • Adi Avram-Shperling, Eli Kopel, Itamar Twersky, Orshay Gabay, Amit BenDavid, Sarit Karako-Lampert, Joshua JC Rosenthal, Erez Y Levanon, Eli Eisenberg, Shay Ben-Aroya. “Identification of Exceptionally Potent Adenosine Deaminases RNA Editors from High Body Temperature Organisms.” PLoS Genetics, 2023.

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