Development of adenoviral vectors armed with TNF-related therapeutic proteins for gene therapy

Gene therapy has enthralled scientists in the last forty years due to its possibility of treating diseases at their genetic origin. The treatment is achieved by delivering genetic material into the patient cells via vectors (e.g., adenovirus).
Through the years, several gene therapies have been developed to treat monogenic diseases (e.g., spinal muscular atrophy [SMA], adenosine deaminase deficiency [ADA]), infectious diseases (e.g., HIV/AIDS, COVID-19), cancer, among others.
Fundamentally, cancer is a genetic disease that has apoptosis evasion and continuous proliferative signaling as main hallmarks. Over the years, the search for new cancer therapeutic proteins with lesser side effects than conventional chemotherapeutic drugs brought to the spotlight the apoptosis-inducing ligands from the tumor necrosis factor (TNF) family, such as TNF-, FasL, and the TNF-related apoptosis-inducing ligand (TRAIL). TRAIL is a protein that is able to selectively induces apoptosis in cancer cells while sparing the healthy cells. Another interesting member from the TNF family with potential therapeutic effects is the receptor activator of NF-B ligand (RANKL). Together with its receptors RANK and OPG due to their involvement in cancer cell migration, including their possible association to fibrosis.
This thesis aims to develop adenoviral vectors armed with TRAIL and RANKL proteins for their use as treatments for cancer or fibrosis.