# Pulmonary endothelium targeted adenoviral gene therapy for the correction of mucopolysaccharidosis type I

> **NIH NIH F31** · WASHINGTON UNIVERSITY · 2024 · $15,972

## Abstract

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.

## Key facts

- **NIH application ID:** 10917085
- **Project number:** 5F31HL165903-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Sarah Hurt
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $15,972
- **Award type:** 5
- **Project period:** 2023-05-01 → 2024-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10917085

## Citation

> US National Institutes of Health, RePORTER application 10917085, Pulmonary endothelium targeted adenoviral gene therapy for the correction of mucopolysaccharidosis type I (5F31HL165903-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10917085. Licensed CC0.

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