The Senate of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) has established the Priority Programme „ Gene and Cell Based Therapies to Counteract Neuroretinal Degeneration” (SPP 2127). The programme is designed to run for six years; the present call invites proposals for the second three-year funding period.

Gene and cell based therapies take centre stage in the attempt to find effective ways to treat rare diseases. Vision loss due to inherited retinal dystrophies is a severe burden for 2–4 million patients worldwide and innovative strategies defeating neuronal dysfunction and cell loss are urgently needed. The current state of the art has advanced quite rapidly in the field of experimental therapies of inherited retinal dystrophies (IRD), with the first drugs approved, clinical trials ongoing for several disorders, and morphological and functional rescue to a certain level evident.

To further improve the development of therapeutic applications in this striving field of science, the results of the first three-year funding period, new data from current trials and preclinical experimentations as well as the improved understanding of the pathology of IRD require continued work at high level.

The major points arising in this striving field can be allocated to four main topics that are closely related and intercalate with each other. They represent the inclusion criteria for participation in the second funding period of the Priority Programme:

(A) Gene based therapies:

• How can we improve efficacy of gene addition approaches in order to restore function to target cells in vivo?
• What is the best way to transfer genes into a large area of the retina? How can we realise pan-retinal gene transfer in human patients?
• How can we improve CRISPR/Cas-based genome editing and gene activation as technologies to efficiently rescue impaired gene function in vivo?
• Can we sufficiently control cellular DNA repair mechanisms in order to ensure safe modifications to the human genome?
• Is it possible to modulate cellular mechanisms/pathways to ameliorate the negative effects of gene defects?

(B) Cell based therapies:

• How can we best obtain, culture and differentiate induced pluripotent stem cells (ipSC) in order to have optimally prepared photoreceptor and retinal pigment epithelium (RPE) cells for transplantation?
• Can human ipSC-derived photoreceptors and RPE cells functionally integrate into the degenerated retina?
• Do 3D retinal cultures (i.e. organoids) represent a potent tool in disease-modelling and therapy development?
• Can we reliably modify the genome in ipSC in a way that autologous re-implantation of differentiated retinal cells becomes a safe approach?

(C) Factors influencing the outcome of gene and cell based therapies:

• How does the retina/RPE/choroid react to treatment with AAV vectors or implantation of photoreceptors and/or RPE cells differentiated from ipSC?
• Since subretinal injections only treat a defined area of the retina, is the remaining untreated area having an impact (potentially negative) on the treatment outcome?
• How do the major glial cells, e.g. Müller cells, and the local immune homeostasis change in the retina/RPE/choroid in response to treatment and how can we modulate these cells to support therapeutic changes?

(D) Read-out parameters:

• Which are early morphological read-out parameters that allow identifying retinal regions that profit most from a gene or cell based therapy?
• How can we measure functional benefit in treated areas in patients with very low level residual function?
• How to detect reliable function in infants and preverbal children not capable to comply with conventional examination tools?

To foster optimal synergy and collaboration between groups, proposals aimed at treating acquired age related disorders of the retina or glaucoma as well as projects focusing on the clinical description of disorders or addressing mainly genotype-phenotype correlations are excluded from the Priority Programme.

Proposals must be written in English and submitted to the DFG by 1 September 2021. Please note that proposals can only be submitted via elan, the DFG’s electronic proposal processing system.

Applicants must be registered in elan prior to submitting a proposal to the DFG. If you have not yet registered, please note that you must do so by 18 August 2021 to submit a proposal under this call; registration requests received after this time cannot be considered. You will normally receive confirmation of your registration by the next working day. Note that you will be asked to select the appropriate Priority Programme call during both the registration and the proposal process.

If you would like to submit a proposal for a new project within the existing Priority Programme, please go to Proposal Submission – New Project – Priority Programmes and select “SPP 2127” from the current list of calls. Previous applicants can submit a proposal for the renewal of an existing project under Proposal Submission – Proposal Overview/Renewal Proposal.

In preparing your proposal, please review the programme guidelines (form 50.05, section B) and follow the proposal preparation instructions (form 54.01). These forms can either be downloaded from our website or accessed through the elan portal. In addition to submitting your proposal via elan, please send an electronic copy to the programme coordinator.

Further Information

More information on the Priority Programme is available under:

• www.spp2127.de

The elan system can be accessed at:

• https://elan.dfg.de/en

DFG forms 50.05 and 54.01 can be found at:

• www.dfg.de/formulare/50_05
• www.dfg.de/formulare/54_01

For scientific enquiries, please contact the Priority Programme coordinator:

• Professor Dr. Knut Stieger
  Justus-Liebig-Universität Gießen
  Fachbereich 11
  Medizin, Klinik und Poliklinik für Augenheilkunde, Experimentelle Ophthalmologie
  Friedrichstraße 18, 35392 Gießen
  phone +49 641 98543835
  knut.stieger@augen.med.uni-giessen.de

For questions related to the DFG review process, please contact:

• Dr. Katja Großmann
  phone +49 228 885-2632
  katja.grossmann@dfg.de

For administrative questions regarding the DFG application, please contact:

• Anna Stinner
  phone +49 228 885-3086
  anna.stinner@dfg.de