ABSTRACT Mucopolysaccharidoses type I (MPS I) is a devastating lysosomal storage disorder that affects approximately 1 in 100,000 newborns. MPS I is characterized by mutations in the α-L-Iduronidase (IDUA) gene that lead to an accumulation of glycosaminoglycans in lysosomes. While treatment is available, it is non-curative, monetarily costly, and time-consuming. To this end, alternative therapies to MPS I have been highly sought after and one such approach is gene therapy. While several vector systems have been explored in the pursuit of a gene therapy treatment for MPS I, adenoviral vectors have been highly understudied. Adenoviral vectors offer several advantages to other vectors such as the ability to transduce both replicating and non-replicating cells, the inability to integrate into the host genome without the use of gene editing technology, and recent modifications leading to the ability to transduce previously unreachable cell types. Thus, investigating the consequences of adenoviral mediated gene therapy for MPS I could lead to new treatment avenues for MPS I. In order to understand the consequence(s) of adenoviral gene therapy for MPS I, I will employ the MPS I murine model and develop an adenoviral vector to deliver the open reading frame for IDUA. I plan to modify our vector using a myeloid-binding peptide to favorably transduce endothelial cells. I hypothesize that a non-liver cellular source can subserve the role of cellular production of IDUA and traverse liver targeting, and, through employment of gene editing technology, long-term correction can be achieved. I will address this hypothesis and achieve the goals of this proposal by employing a myeloid binding peptide modified adenoviral vector expressing IDUA and using in vivo assays to determine IDUA levels in serum post-infection. I will also determine the ability to achieve long-term correction through the use the gene editing technology CRISPR/Cas9. The findings of this proposal will better determine the feasibility of utilizing modified adenoviral vectors as gene therapy vessels and as a treatment method for MPS I and other inherited, monogenic disorders.