Gianluca Petris

Gianluca Petris graduated in medical biotechnology at the University of Trieste; he then obtained a PhD in life and biomolecular sciences awarded by the Open University (Milton Keynes, UK), working at the International Centre for Genetic Engineering and Biotechnology (ICGEB) in Trieste.
After his PhD, he continued his career at CIBIO of the University of Trento, developing genome editing techniques and applying them to gene therapy.
In 2019, he worked at the Medical Research Council Laboratory of Molecular Biology in Cambridge (UK) thanks to a Marie Skłodowska-Curie fellowship, later becoming Principal Scientist at the Wellcome Sanger Institute, also in Cambridge. Here he developed innovative technologies for the creation of synthetic genomes, applied to synthetic biology and the expansion of the genetic code.
In 2024 Petris returned to Italy to join the Department of Medicine at the University of Udine and the Fondazione Italiana Fegato ONLUS, where he founded a new research unit dedicated to biotechnology and genetics applied to the fight against cancer, the Genome Engineering & Biotechnology Unit – GEB Unit

Selected Contributions to Science:

  1. Development and application of a toolbox of CRISPR technologies in the context of genetic diseases and viruses

– Carrozzo et., Functional rescue of F508del-CFTR through revertant mutations introduced by CRISPR base editing. Molecular Therapy (2025) Jan 9:S1525-0016(25)00015-2. https://doi.org/10.1016/j.ymthe.2025.01.011.

– Prakasam et al., LSD1/PRMT6-targeting gene therapy to attenuate androgen receptor toxic gain-of-function ameliorates spinobulbar muscular atrophy phenotypes in flies and mice. Nature Communications (2023), 14 (1):603. https://doi.org/10.1038/s41467-023-36186-9.

– Ambrosini et al., Translational enhancement by base editing of the Kozak sequence rescues haploinsufficiency. Nucleic Acids Research (2022), 50 (18):10756-10771. https://doi.org/10.1093/nar/gkac799.

– Papa et al., CRISPR-Csy4 mediated genome editing of rotavirus dsRNA genome. Cell Reports (2020), 32 (13), 108205. https://doi.org/10.1016/j.celrep.2020.108205.

– Maule et al., Allele specific repair of splicing mutations in Cystic Fibrosis through AsCas12a genome editing. Nature Communications (2019), 10, 3556. https://doi.org/10.1038/s41467-019-11454-9.

– Montagna et al., VSV-G Enveloped vesicles for traceless delivery of CRISPR-Cas9. Molecular Therapy – Nucleic Acids (2018), 12, 453-462. https://doi.org/10.1016/j.omtn.2018.05.010.

– Casini et al., A highly specific SpCas9 variant is identified by in vivo screening in yeast. Nature Biotechnology (2018), 36, 265-271. https://doi.org/10.1038/nbt.4066.

– Petris et al., Hit and go CAS9 delivered through a lentiviral based self-limiting circuit. Nature Communications (2017), 8, 15334. https://doi.org/10.1038/ncomms15334.

  1. Synthetic and Generative Biology methods and applications.

– Zürcher et al., Continuous synthesis of E. coli genome sections and Mb-scale human DNA assembly. Nature (2023), 619 (7970):555-562. https://doi.org/10.1038/s41586-023-06268-1.

– Tang et al., Mechanism-based traps enable protease and hydrolase substrate discovery. Nature (2022), 602 (7898):701-707. https://doi.org/10.1038/s41586-022-04414-9.

– Zürcher et al., Refactored genetic codes enable bidirectional genetic isolation. Science (2022), 378 (6619):516-523. https://doi.org/10.1126/science.add8943.

– Rubio-Sánchez et al., Thermally Driven Membrane Phase Transitions Enable Content Reshuffling in Primitive Cells. Journal of the American Chemical Society (2021), 143 (40):16589-16598. https://doi.org/10.1021/jacs.1c06595.

– Petris. Curing Genetic Diseases through Genome Reprogramming. Progress in Molecular Biology and Translational Science (2021), 182. https://doi.org/10.1016/S1877-1173(21)00133-2.

– Grazioli & Petris. Synthetic genomics for curing genetic diseases. Progress in Molecular Biology and Translational Science (2021), 182, pp. 477–520. https://doi.org/10.1016/bs.pmbts.2021.02.002.

  1. Cancer research

– Alaimo et al., Calcium cytotoxicity sensitizes prostate cancer cells to standard-of-care treatments for locally advanced tumors. Cell Death & Disease (2020), 11 (12), 1039. https://doi.org/10.1038/s41419-020-03256-5.

– Romanel et al., Inherited determinants of early recurrent somatic mutations in prostate cancer. Nature Communications (2017), 8, 48. https://doi.org/10.1038/s41467-017-00046-0.

  1. Developing methods and technologies to investigate or reprogram protein quality control and maturation

– Spagnolli et al., Pharmacological inactivation of the prion protein by targeting a folding intermediate. Communication Biology (2021), 4(1):62. https://doi.org/10.1038/s42003-020-01585-x.

– Cesarattoet al., BiP/GRP78 mediates ERAD targeting of proteins produced by membrane-bound ribosomes stalled at the STOP-codon. Journal of Molecular Biology (2019), 431, 123-141. https://doi.org/10.1016/j.jmb.2018.10.009.

– Cesaratto et al., Tobacco Etch Virus protease: a shortcut across biotechnologies. Journal of Biotechnology (2016), 231:239-49. https://doi.org/10.1016/j.jbiotec.2016.06.012.

– Sasset et al., VCP/p97 and YOD1 proteins have different substrate-dependent activities in endoplasmic reticulum-associated degradation (ERAD). Journal of Biological Chemistry (2015), 290, 28175-88. https://doi.org/10.1074/jbc.M115.656660.

– Cesaratto et al., An engineered Tobacco Etch Virus protease active in the secretory pathway of mammalian cells. Journal of Biotechnology (2015) 212:159-66. https://doi.org/10.1016/j.jbiotec.2015.08.026.

– Petris et al., New Tags for Recombinant Protein Detection and O-Glycosylation Reporters. PLoS ONE 2014, 9 (5): e96700. https://doi.org/10.1371/journal.pone.0096700.

– Petris G et al., CD4 and BST-2/Tetherin Retro-translocate from ER to Cytosol as Partially Folded and Multimeric Molecules. Journal of Biological Chemistry (2014) 289 (1): 1-12. https://doi.org/10.1074/jbc.M113.512368.

–  Vecchi et al., Selective Targeting of Proteins within the Secretory Pathway for Endoplasmic Reticulum-Associated Degradation. Journal of Biological Chemistry (2012) 287, 20007-15. https://doi.org/10.1074/jbc.M112.355107.

– Petris et al., Efficient detection of proteins retro-translocated from the ER to the cytosol by in vivo biotinylation. PLoS One. 2011;6(8):e23712. https://doi.org/10.1371/journal.pone.0023712.

  1. Technology transfer and entrepreneurial activity

As a scientist with a strong technology developer attitude, and recognising the importance and the impact of life sciences in economy and society, Dr. Petris is inventor in several patent families, licensed to national and international companies (e.g. Intellia Therapeutics Inc.), and co-founded the gene editing company Alia Therapeutics srl in 2019.

– 2022 IT-102022000016884, PCT/IT2023/050194. Genome editing of the Kozak sequence for treating diseases.

– 2019  US-62804591, PCT/IB2020/051089. Cas12a guide RNA molecules and uses thereof.

– 2018 IT-102018000007055, PCT/IB2019/055805. Vesicles for traceless delivery of guide RNA molecules and/or guide RNA molecule/RNA-guided nuclease complex(es) and a production method thereof.

– 2017 IT-102017000016321, PCT/EP2018/053717. High-fidelity Cas9 variants and applications thereof.

– 2016 IT-102016000102542, PCT/EP2017/076129. Self-limiting Cas9 circuitry for enhanced safety (SLiCES) plasmid and lentiviral system thereof.

ORCID Identifier: https://orcid.org/0000-0002-2420-6359
Scopus Author ID: 50262698100
Google Scholar: https://scholar.google.com/citations?hl=en&user=TJDlhP0AAAAJ

Active Collaborations:

– Leopold Parts, Genomica Sintetica e Generativa, Wellcome Sanger Institute, Hinxton, United Kingdom.

– Giovanni Sorrentino, Ricerca sul Cancro, Centro Internazione di Ingegneria Genetica e Biotechnologia, Trieste, Italy.

– Julian Sale, Replicazione del DNA, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.

– Charles Lee, Genomica Medica, The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.

– Miriam K Konkel, Genetica Evolutiva, Clemson University, Clemson, SC, USA.

– Claudio Brancolini, Epigenetica, University of Udine, Italy.

– Gianluca Tell, Vescicole Extracellulari, University of Udine, Italy.

– Andrea Dardis, Terapia Genica e Cellulare, University Hospital of Udine, Italy.