IMPROVING THE EFFECTIVENESS
SAFETY OF EPIGENETIC EDITING
BRAIN REGENERATION
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IMPROVING THE EFFECTIVENESS
SAFETY OF EPIGENETIC EDITING
BRAIN REGENERATION
See more
IMPROVING THE EFFECTIVENESS
SAFETY OF EPIGENETIC EDITING
BRAIN REGENERATION
See more
IMPROVING THE EFFECTIVENESS
SAFETY OF EPIGENETIC EDITING
BRAIN REGENERATION
See more
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News & Events

Consortium Meeting of REGENERAR in Coimbra

The meeting gathered all the European partners involved in the project led by the University of Coimbra to develop new technology to regenerate the brain Date: March 22 The first ...
See more

Consortium Meeting of REGENERAR in Coimbra

The meeting gathered all the European partners involved in the project led by the University of Coimbra to develop new technology to regenerate the brain Date: March 22 The first ...
See all

Consortium Meeting of REGENERAR in Coimbra

The meeting gathered all the European partners involved in the project led by the University of Coimbra to develop new technology to regenerate the brain Date: March 22 The first ...
See all

Partners

Description:

The Work Package 6 involves project coordination and management as well as scientific management.

This includes hiring a project manager, elaborating consortium agreements, data management plans, and data exploitation plans, defining management structures such as steering committees, organizing annual face-to-face meetings, coordinating payments to partners, aiding partners with administrative issues, creating and reviewing financial reports, and coordinating reports and deliverables.

Scientific management also involves reviewing scientific outcomes of each work package (WP), ensuring objectives, deliverables, and milestones are met, redirecting project activities if necessary, monitoring project progress through trimestral WP meetings, managing risks, and providing technical reporting.

Description:

The Work Package 5 involves various activities related to communication, dissemination, exploitation, data management, and follow-up after the project’s lifetime.

These activities include recording and reporting dissemination activities, coordinating exploitation efforts to utilize foreground and intellectual property generated during the project, implementing communication and dissemination activities, building a findable, accessible, interoperable and re-usable (FAIR) data platform to collect preclinical data, and defining an exit strategy for the project’s conclusion, identifying future funding opportunities, and connecting with ongoing research and training programs.

Description:

The project will focus on conducting in vivo epigenetic reprogramming experiments using nanoparticles (NPs) loaded with dCas9-VPR protein and specific gRNAs targeting human transgene promoters and neuronal reprogramming factors.

This involves inducing stab wound injuries in adult mice and delivering the NPs to the brain near the injury site via intracerebral administration.

The NPs will be activated by transcranial irradiation, and safety, localization, and epigenome editing capacity will be assessed over time.

Spatial transcriptomics will be performed to evaluate successful in vivo reprogramming of astrocytes into neurons.

Additionally, in vivo epigenetic reprogramming will be conducted using the most effective administration route of the NPs, and whole brain spatial transcriptomics will be performed to confirm any off-target events.

Description:

The Work Package 3 involves several activities related to the generation of reporter mice, epigenetic reprogramming of astrocytes, selection of the route of administration of nanoparticles (NPs), in vivo toxicity assays, and pharmacokinetic and pharmacodynamic studies.

These activities include the use of transgenic mouse lines to analyze and quantify formulation delivery in vivo, isolation and transfection of astrocytes with NPs containing dCas9-VPR protein and gRNAs targeting specific sequences, labeling of NPs with a Cy7 dye to measure accumulation in the brain, in vivo toxicity studies in mice to estimate the toxicological profile of the particles, and pharmacokinetic and pharmacodynamic studies to assess the distribution and effects of the epigenetic reprogramming formulation.

Description:

The Work Package 2 involves several activities related to evaluating and utilising CRISPR/dCas9-loaded nanoparticles (NPs) for gene activation in cells.

These activities include assessing biocompatibility using brain cell lines and peripheral blood mononuclear cells, evaluating NP internalization and intracellular trafficking in primary astrocytes, and testing the capacity of the nanoformulation to induce gene activation by targeting specific genes associated with astrocyte-to-neuron conversion.

Additionally, will be focused on targeting and reprogramming astrocytes in organotypic cortical slice cultures to assess the targeting potential of the NPs and optimize imaging and spatial transcriptomics analyses.

Finally, producing the best NP formulation under Good Laboratory Practice (GLP) conditions will be conducted to ensure regulatory compliance and validate the reliability of non-clinical safety data.

Description:

The Work Package 1 involves various activities related to the preparation and characterization of nanoparticles (NPs) for efficiently delivering the dCas9 protein intracellularly.

It will express the dCas9 protein and prepare polymeric NPs at UC, which are designed to deliver the dCas9 protein effectively inside cells.

Additionally, it will be prepared inorganic NPs, such as gold nanorods (AuNRs), and modified them with oligonucleotides.

These NPs will then be subjected to laser activation to demonstrate the release of the RNP complex, followed by quantification.

Finally, they will characterize the NPs in terms of morphology, charge, RNP loading capacity, stability, and degradation over time.