| Autor: |
Takele Argaw, Michael P. Marino, Andrew Timmons, Lindsey Eldridge, Kazuyo Takeda, Pingjuan Li, Anna Kwilas, Wu Ou, Jakob Reiser |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Molecular Therapy: Methods & Clinical Development, Vol 21, Iss , Pp 670-680 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2329-0501 |
| DOI: |
10.1016/j.omtm.2021.04.012 |
| Popis: |
Despite their exceptional capacity for transgene delivery ex vivo, lentiviral (LV) vectors have been slow to demonstrate clinical utility in the context of in vivo applications. Unresolved safety concerns related to broad LV vector tropism have limited LV vectors to ex vivo applications. Here, we report on a novel LV vector-pseudotyping strategy involving envelope glycoproteins of Tupaia paramyxovirus (TPMV) engineered to specifically target human cell-surface receptors. LV vectors pseudotyped with the TPMV hemagglutinin (H) protein bearing the interleukin (IL)-13 ligand in concert with the TPMV fusion (F) protein allowed efficient transduction of cells expressing the human IL-13 receptor alpha 2 (IL-13Rα2). Immunodeficient mice bearing orthotopically implanted human IL-13Rα2 expressing NCI-H1299 non-small cell lung cancer cells were injected intravenously with a single dose of LV vector pseudotyped with the TPMV H-IL-13 glycoprotein. Vector biodistribution was monitored using bioluminescence imaging of firefly luciferase transgene expression, revealing specific transduction of tumor tissue. A quantitative droplet digital PCR (ddPCR) analysis of lung tissue samples revealed a >15-fold increase in the tumor transduction in mice treated with LV vectors displaying IL-13 relative to those without IL-13. Our results show that TPMV envelope glycoproteins can be equipped with ligands to develop targeted LV vectors for in vivo applications. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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