Objective
Lentiviral vectors can be targeted to specific cell types by varying the envelope proteins, a process called pseudotyping. The rabies-G pseudotyped lentivectors are useful for distal targeting of neurons because they are retrogradely transported to the nucleus where they integrate and express the transgene, as first demonstrated by us. Motor neuron (MN) diseases are incurable neurodegenerative diseases causing progressive paralysis and premature death. Most amyotrophic lateral sclerosis (ALS) cases are sporadic, but there are rare inherited forms one of which being due to mutations in the superoxide dismutase (SOD1) gene. Spinal muscular atrophy (SMA) is the second commonest genetic disease affecting children and is due to mutations in the survival motor neuron (SMN1) gene. In mouse models for ALS (SOD1 mutant mouse) or SMA (SMNDelta7 mouse) when we delivered in various muscle groups rabies-G pseudotyped lentiviral vectors expressing either vascular endothelial growth factor or short interfering RNA targeted to a mutated SOD1 gene or the normal SMN1 gene we corrected motor defects and extended survival. Despite these successes, experiments with rabies-G pseudotyped vectors in non-human primates have failed to give good efficiency of transduction of MNs so as to translate this approach to the clinic. Also SMN-1 targeted replacement produced only a marginal increase in survival despite sparing MNs. In this grant we propose: 1) To investigate the molecular pathway of retrograde transport of the rabies-G lentiviral vectors. This might allow us to increase the efficacy of gene transfer with these vector systems. 2) To design novel lentiviral vectors with tropism to the neuromuscular junction (NMJ) so as to try to increase the efficiency/specificity of gene transfer to MNs. 3) To utilise the new NMJ-targeted lentiviral vector derived in (2) to simultaneously deliver several neuroprotective proteins to MNs and test its efficacy in animal models of ALS and SMA.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences zoology mammalogy primatology
- medical and health sciences medical biotechnology genetic engineering gene therapy
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics mutation
- medical and health sciences basic medicine neurology amyotrophic lateral sclerosis
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback. You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
ERC-2008-AdG
See other projects for this call
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Host institution
SW7 2AZ LONDON
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.