Many interesting and outstanding scientific developments were presented and discussed during the 9th Biennial Meeting of SETGyC, which took place in Mallorca from the 14th to the 16th of March. My main interest was focused on in vivo gene therapy for monogenic diseases and CRISPR/Cas9-based treatments. Both of these topics were discussed during the meeting and I would highlight the fact that most of the gene therapy approaches to treat monogenic disorders are already getting promising therapeutic effects in patients or are on their way to the clinic. Lentiviruses as vectors to treat blood disorders ex vivo were presented by Adrian Trasher (UCL, London, UK), Juan Bueren (CIEMAT, Madrid, Spain) and José Carlos Segovia (CIEMAT, Madrid, Spain) among others. AAVs, on the other hand, were chosen to target the muscle by Fulvio Mavilio (Audentes Therapeutics Inc, San Francisco, CA), the central nervous system by Fatima Bosch (Autonomous University of Barcelona, Spain) and Juan Ruiz (Abeona Therapeutics Inc, Cleveland, OH) and the liver by Gloria González-Aseguinolaza (CIMA and Vivet-Therapeutics, Pamplona, Spain). The excellent short oral presentations at the meeting showed an important trend; all the groups mentioned above and many others are also working in preclinical models to better understand and improve their treatments. This fact highlights the importance of robust basic research to increase the quality and efficacy of the genetic treatments in the clinic. Moreover, exciting new approaches were presented: such as completely new CRISPR/Cas9-based therapies by Paula Río and Francisco José Román-Rodríguez (CIEMAT, Madrid, Spain), and by Francisco Martín and Araceli Aguilar González (Genyo, Granada, Spain); new approaches to treat obesity using AAV by Verónica Jiménez (Autonomous University of Barcelona, Spain), and in utero treatment using lentiviruses to target the liver by Clara Nicolas from Joseph Benjamin Lillegard’s group (Mayo Clinic, Rochester, MN) among others.
Not only did I learn a lot from the presentations of others, I also had the opportunity to discuss my own work with others in the field. At CIMA (Pamplona, Spain), our team is working to develop AAV-based gene therapies for liver metabolic disorders. In the meeting I presented our gene editing project to treat a rare disease called Primary Hyperoxaluria type I (PH1), a devastating disease in which oxalate is overproduced in the liver and accumulated in kidneys. This leads to renal failure during childhood or early adolescence. Our approach consists of the inhibition of an enzyme involved in oxalate synthesis in the liver using CRISPR/Cas9 to target the gene that encodes the enzyme (Figure 1). The use of AAV vectors to express CRISPR/Cas9 system in the liver allows us to apply the treatment in vivo. We have obtained promising results in a PH1 mouse model, which is characterised by the excretion of high oxalate levels in urine and the accumulation of oxalate crystals in renal parenchyma. In the treated animals we have observed a reduction in urine oxalate to normal levels. The animals were also protected against the accumulation of crystals in the kidneys (Figure 1). Importantly, the treatment has shown a safe profile, which encourages us to continue developing the treatment.
Figure 1. Summary of CRISPR/Cas9-based treatment in vivo and the results in the PH1 mouse model.
To present our project in the SETGyC meeting has been a unique opportunity for me for several reasons. Even before arriving at the meeting, I enjoyed preparing the talk and thinking about the best way to communicate in a clear and understandable way. This is really good practice for students. The talk was a great way to present our data. A number of attendees made really positive and helpful comments, which have encouraged me to keep working hard in order to generate new exciting data. Finally, I would like to thank to the SETGyC board for choosing me as a recipient of the Young Investigator Award and to the ESGCT for giving this award. To receive this award in recognition for all the work I have been doing during my PhD means a lot for me, it motivates me to continue with my career and to focus all my efforts in improving as a researcher.