Document Type

Article

Publication Date

12-27-2025

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This article is the author's final published version in Current Issues in Molecular Biology, Volume 48, 2026, Issue 1, Article Number 42.

The published version is available at https://doi.org/10.3390/cimb48010042. Copyright © The Author(s).

Abstract

Mucopolysaccharidosis (MPS IVA) is caused by pathogenic variations in the GALNS gene, leading to the accumulation of glycosaminoglycans in tissues and causing progressive skeletal lesions. While conventional lentiviral vectors (LVs) provide long-term stable expression, they do not deliver therapeutic levels to bone and cartilage. We hypothesized that engineering the LV envelope with a collagen type II-targeting peptide (WYRGRL) increases the binding affinity of the LVs for bone and cartilage. These modified vectors carrying the CBh and COL2A1 promoters delivered the GALNS gene to MPS IVA newborn mice via intravenous (IV) or intraarticular (IA) administration. The peptide-modified LVs exhibited markedly increased uptake in the liver when administered IV, but lower enzyme activity than that of the conventional vector. The modified WYRGRL-LV-COL2A1 vector elevated GALNS activity in other tissues, suggesting systemic benefits. When administered IA, the modified vectors showed potential for local treatment due to the WYRGRL peptide-mediated uptake. Additionally, there was a reduction in keratan sulfate glycosaminoglycan levels in plasma and tissues, indicating that this peptide can be a suitable candidate for disease modification. These findings pave the way for further preclinical and clinical studies, offering new possibilities for the development of targeted therapies for skeletal diseases.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

41614872

Language

English

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