Brain injuries are considered one of the most challenging cases because of the limited ability of neural cells to regenerate. Reprogramming reactive astrocytes, surrounding and within a lesion cavity, into functional neurons through Adeno-associated viruses (AAV) encoding SOX2 or NeuroD1 can provide an alternative therapeutic approach for the regeneration of the injured or diseased brain. However, delivering such AAV, especially into the brain, suffers from challenges like spreading AAV into the non-target tissues, and their neutralisation by the host immune responses.

In this research project, we have developed an injectable hydrogel made of self-assembling peptides (SAPs) that can hold the viral vectors within its nanostructure to keep them in the target tissue and protect them from the host immune responses. Moreover, this hydrogel can be activated by injection of a bio-orthogonal enzyme to release the viral vector. With this technique, we can control the time, location and condition of the viral vectors released in the target tissue.

The optimised sequences of SAPs were synthesised using routine solid-phase peptide synthesis. To characterise the prepared SAPs nanostructures, the samples were tested through Fourier Transform Infrared Spectroscopy (FT-IR), Circular Dichroism (CD), Transmission Electron Microscopy (TEM) and Zeta potential assay. Their functionality in response to the enzyme was also tested. The enzyme will ensure precise gene delivery timing by cleaving only the delivery systems holding the viral vector. The biocompatibility of this system was also tested in contact with the primary astrocytes.