Purpose of the project:

Designing, evaluating the safety and effectiveness of the preclinical gene therapy study of hereditary retinal diseases in order to provide conditions for entering the clinical phases of gene therapy.

The target community that will benefit from this project and the need to do:

With the increase of knowledge in the pathobiological basis of various diseases and the advancement of gene transfer technology during the last two decades, gene therapy has been considered as a realistic treatment solution. If the evidences in the gene therapy studies registered in the clinical phases show that the eye is especially a suitable target for gene therapy. The favorable features of the eye for this type of studies include the availability of the eye and its structure, which allows small amounts of local injection of biological agents to be done by direct observation and without invasive methods. This local injection reduces the side effects that may occur due to systemic administration of the drug. Another desirable feature is specific immunity, which is created due to blood-eye barriers. And of course, the improvement of vision in the involved people is of great importance for the patients, their families and finally the society.

Hereditary retinal diseases such as Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP) are among the most active fields of eye gene therapy. These diseases are one of the main causes of blindness in the world, but currently there is no cure for them. In this project, we plan to conduct preclinical studies for gene therapy by lentiviral vectors for one of the two candidate genes for hereditary retinal diseases. These genes have been identified based on the results of the genetic examination of a part of the patients registered in the National Registry of Hereditary Retinal Diseases in Iran. Lentiviral vectors are used in this study and due to the relatively large size of the target genes of this study, the use of these vectors is important. In addition, these vectors have the possibility of transferring to non-dividing differentiated cells such as photoreceptors (which are the target cells of this study) as well as proliferating cells. Our research program will be an intermediary between basic science and clinical applications, and the findings will definitely provide a platform for future design and planning of treatment methods related to hereditary retinal diseases, and perhaps be used as a model for the initiation of gene therapy for other diseases. This project will be carried out as a joint collaboration between the Eye Research Center of Shahid Beheshti University of Medical Sciences, the Faculty of New Technologies of Shahid Beheshti University of Medical Sciences, and the Pathology and Immunology Department of the University of Geneva, Switzerland.

Output and achievements of the project:

Design of lentiviral vectors carrying alternative healthy genes
Investigating the safety of viral constructs in cell culture medium and retinal tissue
Investigating the effectiveness of viral constructs in cell culture medium and retinal tissue
Animal studies investigating the safety and effectiveness of viral constructs in histopathology, electroretinography and functional studies
Providing the conditions to enter the clinical phases of gene therapy for this category of patients in the future

Executive agents of the project:

Dr. Hamid Ahmadieh, Dr. Fateme Souri, Dr. Mozhgan Rezaei Kanvi, Dr. Javad Ranjbari, Dr. Azam Rahimpour, Mr. Sajjad Najafi, Dr. Karl-Heinz Krause, Dr. Marco Alessandrini, Dr. Stylianos Antonarakis

The platform of the project or the executive body:

Shahid Beheshti University of Medical Sciences Eye and Vision Research Institute, Shahid Beheshti University of Medical Sciences Faculty of Modern Technologies and Department of Pathology and Immunology, University of Geneva, Switzerland