IrsiCaixa carries out a 1M € project for the development of gene therapy against HIV

CCR5-Delta32 mutation is a rare blood disorder that affects approximately 1% of the European population. It is known that people who have this gene mutation are naturally resistant to HIV, because it prevents the virus from entering its target cells, CD4 T lymphocytes. An academy-company consortium made up of 4 Spanish entities carries out a project funded with 942,000€ by the Spanish Ministry of Economy. The project, Stop AIDS, aims to develop a gene therapy to reproduce this mutation in the cells of HIV-infected people, in order to cure them. The four entities are IrsiCaixa AIDS Research Institute, the Consejo Superior de Investigaciones Científicas (CSIC), Karuna Good Cell Technologies, S.L., and Praxis Pharmaceutical, S.A.

The first phase of the project, led by the CSIC, will use the latest developments in genomic editing, patented by some of the members of the consortium (GURAIZEAK©), to modify in vitro the CD4 T lymphocytes of HIV-infected people, preventing them from expressing the protein. Scientists have already shown in previous studies that this protein can be manipulated without damaging the patient, as it is not necessary for cell survival.

Infusion of these modified cells would allow patients to have a certain percentage of HIV-resistant CD4+ T lymphocytes. However, the percentage of resistant cells could be increased by using hematological stem cells. For this reason, a second phase will consist of isolating stem cells from the patient, inactivating the gene and transferring them back to the patient (an autologous transplantation, in which donor and recipient are the same person). This way, scientists expect to get a permanent HIV-resistant immune system.

Design and application of a clinical trial

The project plans in vitro and animal studies during 3 years, to determine the safety and efficacy of the procedure. "One of the great challenges is to modify cells from a genetic point of view and to make them proliferate in vitro to reinfuse them in patients," explains Dr. Javier Martínez-Picado, a ICREA researcher professor at IrsiCaixa.

Dr. Daniel Bachiller, senior scientist of the CSIC at the Mediterranean Institute for Advanced Studies (IMEDEA) in Mallorca (Spain), highlights the huge transformation that medicine will experience with the application of new genome editing technologies: "Thanks to them, it will be possible to repair genes, eliminate hereditary defects and even add new capabilities."

Once the analyzes are completed, Karuna and Praxis will produce this technology under GMP (Good Manufacturing Practices) conditions, to guarantee the safety of its application in humans. The final phase of the project includes the design and application for a phase I/II clinical trial.