SPP 2127:  Gene and cell based therapies to counteract neuroretinal degeneration

• Subject Area: Medicine ; Biology
• Term: since 2018
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 360003551

The research priority program SPP2127 aims at developing gene and cell based therapies to treat inherited retinal diseases. Not only new approaches in both field will be worked at but scientist are also characterizing factors influencing the outcome of the therapy and develop new clinical readout parameter for subsequent use in clinical trials.The coordination fonds aims at supporting networking and cooperation between the different groups funded within the SPP. A major goal is to support young scientists. These goals will be accomplished by organizing meetings, summer schools and lab exchanges as well as by providing seed funding for two new projects. Funding for gender equality measures is available upon request to support female scientists.

• DFG Programme: Priority Programmes

Projects

• A multiplexing CRISPRa approach for gene-independent therapy of retinal degeneration (Applicant Biel, Martin )
• Adaptive optics imaging and micro-stimulation to yield in vivo single-cell biomarker of retinal function and dysfunction in the human retina. (Applicant Harmening, Wolf )
• Adaptive optics retinal camera in retinal neurodegeneration: novel morphological read-out parameters and retinal cellular & vascular reaction following the therapy (Applicant Stingl, Katarina )
• Barrier free chromatic pupillometry in children from infancy on. A novel biomarker to quantify outer and inner retinal function in inherited retinal disorders as a measure of therapeutic benefit after gene therapy. (Applicant Lorenz, Birgit )
• Coordination Funds (Applicant Stieger, Knut )
• Correcting a common CRB1 mutation by RNA base editing – towards an unprecedented treatment strategy for retinal degeneration (Applicants Achberger, Kevin ;  Stafforst, Thorsten )
• CRISPR/Enhanced-Deletion Cas9-mediated allele-specific targeting of the rhodopsin gene: a novel mutation-independent approach to treat RHO-linked autosomal dominant Retinitis pigmentosa (Applicant Wissinger, Bernd )
• Defining donor-host interactions to improve photoreceptor replacement therapy (Applicant Ader, Marius )
• Developing patient-relevant outcome measures for clinical trials of sight-restoring interventions in very low and ultra-low vision (Applicant Finger, Ph.D., Robert Patrick )
• Developing patient-reported outcome measures for children and teenagers for clinical trials of sight-restoring interventions in very low and ultra-low vision (Applicant Finger, Ph.D., Robert Patrick )
• Evaluating the role and therapeutic potential of cytoskeletal dysregulation in CRB1-linked retinal degenerations (Applicants Liebau, Stefan ;  Ueffing, Ph.D., Marius )
• evaluating the therapeutic potential of gene editing in a pig model with a dominant negative mutation in the GUCY2D gene (Applicants Giesert, Florian ;  Klymiuk, Nikolai )
• Gene therapy with designed splice factors to correct splicing defects in Rd6 mice (Applicant Neidhardt, John )
• Identification and characterization of ciliary WNT inhibitors to improve RPE maturation and function (Applicant May-Simera, Ph.D., Helen )
• Manipulation of ciliary WNT signalling to improve RPE maturation in vivo and in vitro. (Applicant May-Simera, Ph.D., Helen )
• Modeling of early-onset retinal dystrophy development in optic vesicle containing-brain organoids (Applicants Gopalakrishnan, Ph.D., Jay ;  Nagel-Wolfrum, Kerstin )
• Novel adeno-associated virus (AAV) vectors for improved retinal gene therapy (Applicant Michalakis, Stylianos )
• Optimization of treatment flow to improve performance of retinal gene therapy (Applicant Seeliger, Mathias )
• Optimizing outcome parameters of photoreceptor- and post-receptoral-specific function for clinical trials in patients with inherited retinal diseases (Applicant Huchzermeyer, Cord )
• Optimizing photoreceptor cell replacement therapies in human retinal pathology models: mechanisms of cell integration (Applicant Karl, Mike O. )
• Overcoming innate immunity towards genetic therapies in the eye (Applicant Fischer, Ph.D., M. Dominik )
• Pathway engineering to optimize homology dependent therapeutic genome editing at the ABCA4 locus in photoreceptors (Applicants Busskamp, Ph.D., Volker ;  Stieger, Knut )
• Programming retinal Müller glial cells for supporting neuronal survival in retinal degeneration (Applicants Deeg, Cornelia ;  Hauck, Stefanie M. )
• Re-engineering melanopsin as a tool for optogenetic vision restoration (Applicant Lindner, Moritz )
• Selecting the right patients for gene-based therapies: Development and implementation of a pathogenicity scoring system combined with functional in vitro validation of gene variants and genotypes in patients with inherited retinal dystrophy as a criterion for the eligibility for therapeutic studies (Applicant Kohl, Susanne )
• Targeting Müller cells for complement modulating gene addition therapy in a mouse model for Stargardt disease type 1 (Applicants Grosche, Antje ;  Pauly, Diana )
• USH1C porcine model utilisation: assessing the function of USH1C/harmonin in the retina and conducting preclinical AAV-mediated gene augmentation therapy in the eye (Applicants Klymiuk, Nikolai ;  Wolfrum, Uwe )

• Spokesperson: Professor Dr. Knut Stieger