‘Nature Communications’ publishes new gene writing technology to allow for more effective and safe advanced therapies
Developed by researchers at the Translational Synthetic Biology Lab at the Pompeu Fabra University (UPF) led by Dr Marc Güell. UPF has transferred the technology to Integra Tx.
9 December 2021
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
Integra Therapeutics secures €4.5-million in funding from Advent France Biotechnology, Invivo Capital and Takeda Ventures
The investment will be used to develop an innovative gene writing platform with the potential to make advanced therapies safer and more effective
Dr Marc Güell and Dr Avencia Sánchez-Mejías, co-founders of Integra Tx
2 December 2021
Integra Therapeutics, a biotechnology company that is creating next-generation gene writing tools to boost the efficiency and safety of advanced therapies, has completed its first round of funding for €4.5 million with Advent France Biotechnology (France), Invivo Capital (Spain) and Takeda Ventures (USA).
Integra Tx was founded in late 2020 as a spin-off of Pompeu Fabra University (UPF) based on technology developed in the Translational Synthetic Biology Lab led by Dr Marc Güell (EMBO Young Investigator, National Research Award for Young Talent and co-founder of two biotech firms).
The great potential of this novel gene writing technology lies in the fact that it resolves some of the main technical limitations of gene therapy: it can be used to paste DNA sequences of any size gene with high precision. Advanced therapies are one of the pillars of the medicine of the future and are aimed at both preventing and treating genetic and oncological diseases that, for now, are incurable.
The funds raised in this round will allow Integra Tx to complete the prototype of the new gene writing technology platform, carry out preclinical validation using in vivo and ex vivo models, and manage its patent portfolio in 2022 and 2023. After that, the company plans to open a Series A round to seek regulatory approval and carry out clinical trials with patients.
“We’re very proud to be transferring our scientific knowledge and technological skills in gene editing from the lab to society. We thank all our investors for their commitment to Integra Tx and to making advanced therapies safer and more effective, and getting them to patients that urgently need them,” says Dr Avencia Sánchez-Mejías, co-founder and CEO of Integra Tx. Sánchez-Mejías joined the UPF Translational Synthetic Biology Lab in 2018 after doing research at the Institute of Biomedicine of Seville, the National University of Singapore and the University of Miami Miller School of Medicine.
Dr Marc Güell, co-founder and CSO of Integra Tx, explains, “the Integra Tx technology platform is very promising because it is an evolution of the CRISPR-Cas techniques. We’ve found a way to merge them with transposase and integrase proteins that have a great capacity for gene transfer and to not depend on viral vectors for transporting the components into the cell, which is a step forward in making these therapies safer.” Plus, it has applications both in vivo (directly in patients) and ex vivo (outside of patients).
Matthieu Coutet, Managing Partner at Advent France Biotechnology, adds: “We decided to invest in Integra Tx because we believe in its seasoned scientific and management team. Its founders have shown a strong passion and ambition to move Integra Tx’s technology forward, combined with a proven expertise in gene editing and advanced therapies.”
Dr Luis Pareras, Managing Partner at Invivo Capital, says: “We’re thrilled with the possibilities Integra Tx’s plataform can develop to solve the problem of cargo size in gene therapy. We’re also very pleased with the international syndicate supporting this seed round, in yet another example of technology transfer opportunity and the competitiveness of the biotech ecosystem in Spain.”
Miles Gerson, Takeda Ventures Partner and Senior Investment Director, says: “Takeda Ventures is very excited to support Integra Tx and their next generation gene writing platform with many potential applications to benefit patients.”