Grant: Project Grant

Several diseases are the consequence of one or more mutations in the genetic material of the cells that constitute organs. In some cases, these mutations take place in DNA regions coding for proteins, such as enzymes, leading to the formation of altered proteins that are uncapable of expressing their activity, that in turn can lead to dangerous pathological alterations. For instance, this is what happens in case of mutations to the gene coding for the enzyme called lysosomal acid lipase, responsible of the degradation of certain lipids within the cells. Due to this alteration, lipids tend to accumulate in vital organs of the body, leading to severe diseases. Unfortunately, currently, the only effective treatment is based on weekly infusions of recombinant enzyme, a strategy that have several limitations. Above all, the enzyme has a limited ability to reach the organ of interest, requires weekly infusion during the whole life of a patient, and promote the generation of neutralizing antibodies. With this project we will explore the development of nanoparticles for the effective delivery of a new class of drug, based on nucleic acid, able to stimulate the cells to recover the missing enzyme over a long period of time, thus effectively eliminate the lipids and prevent the diseases symptoms while eliminating the need of frequent infusions. This will provide a valid alternative for the management of this severe and rare disease.