Gelatin methacryloyl (GelMA) microporous annealed particle (MAP) scaffold for non-viral vector delivery

Abstract

Gene therapy is a therapeutic strategy based on the intracellular delivery of genetic material (DNA or RNA). It is particularly promising to treat severe diseases for which the pathophysiology and genetic targets are known, e.g., cancer. In general, the success of gene therapy depends on (I) the protection of genetic material against nuclease-mediated degradation in the body fluids and (II) safe site-specific intracellular delivery without any cytotoxic effects. As a promising alternative, genetic materials can be complexed with cationic materials in supramolecular structures, e.g., non-viral vectors. The main challenge associated with the development of non-viral carriers is the design of efficient nanoscale delivery systems that can provide high levels of gene transfer and protection of the genetic cargo in the biological environment. Another major challenge of gene therapy lies in developing approaches for local gene delivery in which direct intra-articular injection is not appropriate for targeting a specific tissue. For this purpose, the development of gene-activated matrices (GAMs) has been explored to achieve controlled and localized gene expression in tissue engineering and regenerative medicine. Combining 3D matrices or scaffolds with gene therapy can guarantee prolonged delivery of the genetic materials and a more confined and localized effect of overexpression. In the perspective of tissue engineering, the research group led by Prof. Ali Khademhosseini has developed a novel scaffold known as GelMA microporous annealed particle (MAP) hydrogel. Interest in microporous scaffolds has arisen due to the lack of pore interconnectivity in traditional "bulk" hydrogels, inhibiting cell elongation and migration. However, GelMA MAP scaffolds have not been investigated so far as a gene-activated matrix. Hence, this research proposal involves undertaking an internship in the Khademhosseini group to learn about GelMA hydrogels and MAP techniques. Furthermore, we will investigate the possibility of coupling non-viral vectors to deliver model pDNA. In this project, we will also compare the transfection assay in two modes (i) "bulk" hydrogels and (ii) beaded GelMA (MAP scaffolds). Therefore, this project will contribute to (I) increasing the knowledge in our research group in the field of nanotechnology, tissue engineering, and microfluidics, (II) facilitate the development of new approaches for gene therapy, e.g., the use of advanced scaffold as a gene-activated matrix. (AU)