A multidisciplinary and international team of researchers from the Translational Synthetic Biology Lab at the Pompeu Fabra University (UPF), led by Dr Marc Güell, publishes an article in the scientific journal Nature Communications which shows the potential of the Find Cut-and-Transfer (FiCAT) technology as a state-of-the-art gene writing tool to develop advanced therapies that are more effective and safe in its future clinical application in patients with genetic and oncological diseases currently incurable.
The UPF’s Translational Synthetic Biology Lab has been working in gene editing and synthetic biology applied to gene therapies since 2017. The FiCAT technology is an important scientific advancement to overcome the limitations of the CRISPR-Cas genome editing technique.
“Engineering of the human genome has advanced significantly in the past decade with the development of new editing tools, but there was still an unmet need for technology to allow for therapeutic genes to be transferred efficiently without size limitations”, says Dr Marc Güell, the lead author of the study.
In this work, researchers develop an efficient and precise programmable gene writing technology based on an engineered Cas9 and piggybac (PB) transposase fusion protein with capability to deliver small and large payloads. They test the technology in cellulo achieving on-target efficiencies of 5–22% with low or absent off-target events and they have demonstrated on-target gene transfer in vivo to mice liver, as well as germline cells in mouse models. Finally, they perform directed evolution of FiCAT and further improved efficiency by 25–30%.
The UPF has transferred the FiCAT technology to Integra Therapeutics, founded in 2020 by the researchers Marc Güell and Avencia Sánchez-Mejías.
‘’Our goal is to transfer our scientific knowledge and technological capacity to the biopharmaceutical industry in order to develop efficient, safe advanced technologies, that in turn will reach the patients’’ says Dr Avencia Sánchez-Mejías, co-corresponding author of the manuscript and CEO of Integra Tx. Recently, Integra Tx secured €4.5-million in funding from AdBio Partners (France), Invivo Capital (Spain) and Takeda Ventures (USA).
The work published in Nature Communications was conducted with funding from the European Commission UPGRADE-Horizon 2020 programme; the Spanish State Research Agency (AEI) Retos de la Sociedad programme; the AGAUR Producte grants; the CaixaImpulse Validate and CaixaImpulse Consolidate programmes of “la Caixa”; the Fundación Ramón Areces, and the Ramón y Cajal programme of Spain’s Ministry of Economy, Industry and Competitiveness.
Pallarès-Masmitjà, M; Ivančić, D; Mir-Pedrol, J; Jaraba-Wallace, J; Tagliani, T; Oliva, B; Sánchez-Mejías, A; Güell, M. Find and cut-and-transfer (FiCAT) mammalian genome engineering. Nature Communications (2021). DOI: https://doi.org/10.1038/s41467-021-27183-x