Syndecan-4 Mediates the Cellular Entry of Adeno-Associated Virus 9
Due to their low pathogenicity, immunogenicity, and long-term gene expression, adeno-associated virus (AAV) vectors emerged as safe and efficient gene delivery tools, over-coming setbacks experienced with other viral gene delivery systems in early gene therapy trials. Among AAVs, AAV9 can translocat...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2023
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| Sorozat: | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
24 No. 4 |
| Tárgyszavak: | |
| doi: | 10.3390/ijms24043141 |
| mtmt: | 33630992 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/26461 |
| LEADER | 02845nab a2200301 i 4500 | ||
|---|---|---|---|
| 001 | publ26461 | ||
| 005 | 20230209095311.0 | ||
| 008 | 230209s2023 hu o 0|| Angol d | ||
| 022 | |a 1661-6596 | ||
| 024 | 7 | |a 10.3390/ijms24043141 |2 doi | |
| 024 | 7 | |a 33630992 |2 mtmt | |
| 040 | |a SZTE Publicatio Repozitórium |b hun | ||
| 041 | |a Angol | ||
| 100 | 1 | |a Hudák Anett | |
| 245 | 1 | 0 | |a Syndecan-4 Mediates the Cellular Entry of Adeno-Associated Virus 9 |h [elektronikus dokumentum] / |c Hudák Anett |
| 260 | |c 2023 | ||
| 300 | |a 17 | ||
| 490 | 0 | |a INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES |v 24 No. 4 | |
| 520 | 3 | |a Due to their low pathogenicity, immunogenicity, and long-term gene expression, adeno-associated virus (AAV) vectors emerged as safe and efficient gene delivery tools, over-coming setbacks experienced with other viral gene delivery systems in early gene therapy trials. Among AAVs, AAV9 can translocate through the blood-brain barrier (BBB), making it a promising gene delivery tool for transducing the central nervous system (CNS) via systemic administration. Recent reports on the shortcomings of AAV9-mediated gene delivery into the CNS require reviewing the molecular base of AAV9 cellular biology. A more detailed understanding of AAV9’s cellular entry would eradicate current hurdles and enable more efficient AAV9-based gene therapy approaches. Syndecans, the transmembrane family of heparan-sulfate proteoglycans, facilitate the cellular uptake of various viruses and drug delivery systems. Utilizing human cell lines and syndecan-specific cellular assays, we assessed the involvement of syndecans in AAV9’s cellular entry. The ubiquitously expressed isoform, syndecan-4 proved its superiority in facilitating AAV9 internalization among syndecans. Introducing syndecan-4 into poorly transducible cell lines enabled robust AAV9-dependent gene transduction, while its knockdown reduced AAV9’s cellular entry. Attachment of AAV9 to syndecan-4 is mediated not just by the polyanionic heparan-sulfate chains but also by the cell-binding domain of the extracellular syndecan-4 core protein. Co-immunoprecipitation assays and affinity proteomics also confirmed the role of syndecan-4 in the cellular entry of AAV9. Overall, our findings highlight the universally expressed syndecan-4 as a significant contributor to the cellular internalization of AAV9 and provide a molecular-based, rational explanation for the low gene delivery potential of AAV9 into the CNS. | |
| 650 | 4 | |a Klinikai orvostan | |
| 700 | 0 | 1 | |a Roach Matthew |e aut |
| 700 | 0 | 1 | |a Pusztai Dávid |e aut |
| 700 | 0 | 2 | |a Pettkó-Szandtner Aladár |e aut |
| 700 | 0 | 2 | |a Letoha Annamária |e aut |
| 700 | 0 | 2 | |a Szilák László |e aut |
| 700 | 0 | 2 | |a Azzouz Mimoun |e aut |
| 700 | 0 | 2 | |a Letoha Tamás |e aut |
| 856 | 4 | 0 | |u http://publicatio.bibl.u-szeged.hu/26461/1/Hudak.pdf |z Dokumentum-elérés |