Project Details
Project Description
In exciting recent work, we have cloned the single-chain variable fragment (scFv) of our lead tau-specific mAb into an AAV expression vector and packaged the vectored antibody into AAV. Following transduction of primary neurons, we demonstrated successful expression of the tau scFv within neurons. Furthermore, we found that the tau scFv was able to bind to tau in the cytoplasm, demonstrating for the first-time intracellular tau engagement with a tau-specific antibody. We now seek to determine whether functional, intracellular scFvs can be expressed within neurons following treatment with scFv-mRNA, encapsulated within lipid nanoparticles (LNP). To do so, we will use mouse primary hippocampal neurons and our in-house tau aggregation cell assay, to characterise the expression of the tau scFv following mRNA-LNP treatment, as well as the ability of the intracellular tau scFv to engage intraneuronal tau and prevent its aggregation. Finally, the ability of the tau scFv to be expressed in vivo will be determined following intrathecal administration of the scFv-mRNA-LNP of wild-type mice.
Status | Active |
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Effective start/end date | 21/07/23 → 31/12/25 |
Keywords
- Alzheimer's Disease
- mRNA