Overview
Genome editing technologies are transforming medical science and redefining therapeutic approaches for a broad spectrum of diseases, including genetic disorders, cancer and infectious diseases.
In our laboratory we focus on developing novel genome editing technologies by identifying new RNA-guided nucleases and enhancing their function in mammalian cells through directed evolution and rational molecular engineering. These projects enable us to uncover key molecular determinants driving efficient and precise genome editing in mammalian cells. Our discoveries are translated into therapeutic applications by integrating advanced genome editing technologies with optimized delivery systems. We have a second not less important focus consisting in developing gene therapy strategies for cystic fibrosis through the development of genome editing strategies and new delivery tools.
Research directions
- Metagenomic analysis for the discovery of a diverse range of programmable RNA-guided nucleases
In collaboration with Laboratory of Computational Metagenomics we are searching for novel RNA guided nucleases to advance genome editing for the treatment of genetic diseases. Discovering new tools is crucial to overcoming current limitations in therapeutic applications including inefficient delivery caused by large molecular size of existing genome editing tools, and the restricted range of genomic targets due to the sequence specificity of RNA guided protein. The successful advancement of genome editing for therapeutic applications depends on expanding of the genome editing toolbox to address the complexity of gene therapy across a wide variety of diseases.
- Optimization of genome editing tools for genome editing applications in mammalian cells
The majority of genome editing tools originate from prokaryotes necessitating adaptation for functionality within the eukaryotic nuclear environment. In our lab, we have developed a directed evolution platform in eukaryotes that enhances both the specificity and efficiency of the genome editing tools. This approach is complemented by molecular engineering informed by the structural analysis of the proteins and their associated RNA. The insights gained from these optimization processes are crucial to our understanding of RNA guided nuclease biology and will accelerate the development of next-generation genome editing tools.
- Gene therapy for cystic fibrosis
Cystic fibrosis (CF) is one of the most common inherited lethal diseases, affecting over 160,000 patients world wide. While pharmacological treatments improved health and quality of life for many people with CF, these therapies are not curative and often come with side effects. Moreover a subset of CF mutations remains untreatable with current drugs. Our lab is dedicated to developing strategies to correct CF mutations either on individual basis or through a universal “one strategy for all” approach. Additionally, we focus on developing efficient delivery systems to enable for a safe and effective definitive cure.
Group members
- Anna Cereseto, PI
- Ilaria Bonuzzi, PhD student
- Enrica Brugnara, Postgraduate fellow
- Matteo Ciciani, PhD student
- Alessio Conci, Post Doc student
- Elena Gurrieri, Post Doc student
- Eyemen Kheir, Post Doc student
- Giulia Maule, Post Doc student
- Federica Marelli, Post Doc student
- Daniele Menghini, Postgraduate fellow
- Pau Marin Escudero, PhD student
- Giulia Vittoria Ruta, Post Doc studente
- Alice Setti, Lab Manager
- Marta Stancampiano
- Alessandro Umbach, Post Doc student
- Marta Zoccheddu, PhD student
- Francesca Zerbini, Program Manager
Collaborations
- Marianne Carlon, KU Leuven, Belgium
- Luis Galietta, TIGEM, Italy
- Giuseppe Ronzitti, Genthon, France
- Gloria Gonzales Aseguinolaza, Cima Universidad de Navarra, Spain
Funding
MyBET - Funding Italian for Science – Italian Ministry of University and research
AAVolution - European Commition for Innovatioan (EIC)
GenDel-CF Italian Cystic Fibrosis Fundation
GET-IN European Commission (MSCA Doctoral Network)