Neuronal Replenishment via Hydrogel-Rationed Delivery of Reprogramming Factors

• DOI: 10.1021/acsnano.3c11337
• Publication Date: 2024-01-15T06:04:08Z
• Authors: Negar Mahmoudi; Yi Wang; Niamh Moriarty; Noorya Y. Ahmed; Nathalie Dehorter; Leszek Lisowski; Alan R. Harvey; Clare L. Parish; Richard J. Williams; David R. Nisbet
• Keywords: Reprogramming; Regenerative Medicine

The central nervous system's limited capacity for regeneration often leads to permanent neuronal loss following injury. Reprogramming resident reactive astrocytes into induced neurons at the site of injury is a promising strategy neural repair, but challenges persist in stabilizing and accurately targeting viral vectors transgene expression. In this study, we employed bioinspired self-assembling peptide (SAP) hydrogel precise controlled release hybrid adeno-associated virus (AAV) vector, AAVDJ, carrying NeuroD1 reprogramming transgene. This method effectively mitigates issues high dosage target site, off-target delivery, immunogenic reactions, enhancing vector's efficiency. vitro, vector successfully neuron formation, as confirmed by morphological, histochemical, electrophysiological analyses. vivo, SAP-mediated delivery AAVDJ-NeuroD1 facilitated trans-differentiation host neurons, concurrently reducing glial scarring. Our findings introduce safe effective treating system injuries, marking significant advancement regenerative neuroscience.