Multi-component polymeric system for tumour cell-specific gene delivery using a universal bungarotoxin linker.
PURPOSE: A new universal tool for specific, non-covalent and non-destructive attachment of a recombinant antibody fragment to a polymer-modified adenovirus has been utilised to regulate the tropism of adenoviral gene delivery vector. METHODS: We have prepared a multivalent reactive N-(2-hydroxypropy...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2010
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| _version_ | 1797098339997581312 |
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| author | Willemsen, R Pechar, M Carlisle, R Schooten, E Pola, R Thompson, A Seymour, L Ulbrich, K |
| author_facet | Willemsen, R Pechar, M Carlisle, R Schooten, E Pola, R Thompson, A Seymour, L Ulbrich, K |
| author_sort | Willemsen, R |
| collection | OXFORD |
| description | PURPOSE: A new universal tool for specific, non-covalent and non-destructive attachment of a recombinant antibody fragment to a polymer-modified adenovirus has been utilised to regulate the tropism of adenoviral gene delivery vector. METHODS: We have prepared a multivalent reactive N-(2-hydroxypropyl)methacrylamide-based copolymer (PHPMA) bearing an α-bungarotoxin-binding peptide (BTXbp). The copolymer was used for covalent surface modification of adenoviral vectors (Ad). The α-bungarotoxin protein (BTX) has a nanomolar binding affinity for BTXbp, allowing non-covalent linkage of BTX fusion proteins. A single chain variable fragment of anti-PSMA antibody bearing BTX (scFv-BTX) binding to the prostate-specific membrane antigen (PSMA) was conjugated with the copolymer-coated adenovirus to enable specific infection of prostate cancer cells via PSMA receptors. RESULTS: As shown by ELISA, the copolymer-coated virus exhibited much reduced binding to anti-Ad antibodies. Infection of PC-3 and LNCaP prostate cancer cells was ∼100-fold less efficient with copolymer-coated Ad than with un-modified Ad. Conjugation of scFv-BTX with Ad-PHPMA-BTXbp led to 5-10-fold restoration of infection in PSMA-positive LNCaP cells. In PSMA-negative PC-3 cells, the conjugation of scFv-BTX with Ad-PHPMA-BTXbp gave no enhancement of infection. CONCLUSIONS: We have shown that the presented Ad-PHPMA-BTXbp/scFv-BTX system can be used as a universal tool for a receptor-specific virotherapy. |
| first_indexed | 2024-03-07T05:08:07Z |
| format | Journal article |
| id | oxford-uuid:daa1a857-0031-4a2d-9be5-3151367ab248 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:08:07Z |
| publishDate | 2010 |
| record_format | dspace |
| spelling | oxford-uuid:daa1a857-0031-4a2d-9be5-3151367ab2482022-03-27T09:04:32ZMulti-component polymeric system for tumour cell-specific gene delivery using a universal bungarotoxin linker.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:daa1a857-0031-4a2d-9be5-3151367ab248EnglishSymplectic Elements at Oxford2010Willemsen, RPechar, MCarlisle, RSchooten, EPola, RThompson, ASeymour, LUlbrich, KPURPOSE: A new universal tool for specific, non-covalent and non-destructive attachment of a recombinant antibody fragment to a polymer-modified adenovirus has been utilised to regulate the tropism of adenoviral gene delivery vector. METHODS: We have prepared a multivalent reactive N-(2-hydroxypropyl)methacrylamide-based copolymer (PHPMA) bearing an α-bungarotoxin-binding peptide (BTXbp). The copolymer was used for covalent surface modification of adenoviral vectors (Ad). The α-bungarotoxin protein (BTX) has a nanomolar binding affinity for BTXbp, allowing non-covalent linkage of BTX fusion proteins. A single chain variable fragment of anti-PSMA antibody bearing BTX (scFv-BTX) binding to the prostate-specific membrane antigen (PSMA) was conjugated with the copolymer-coated adenovirus to enable specific infection of prostate cancer cells via PSMA receptors. RESULTS: As shown by ELISA, the copolymer-coated virus exhibited much reduced binding to anti-Ad antibodies. Infection of PC-3 and LNCaP prostate cancer cells was ∼100-fold less efficient with copolymer-coated Ad than with un-modified Ad. Conjugation of scFv-BTX with Ad-PHPMA-BTXbp led to 5-10-fold restoration of infection in PSMA-positive LNCaP cells. In PSMA-negative PC-3 cells, the conjugation of scFv-BTX with Ad-PHPMA-BTXbp gave no enhancement of infection. CONCLUSIONS: We have shown that the presented Ad-PHPMA-BTXbp/scFv-BTX system can be used as a universal tool for a receptor-specific virotherapy. |
| spellingShingle | Willemsen, R Pechar, M Carlisle, R Schooten, E Pola, R Thompson, A Seymour, L Ulbrich, K Multi-component polymeric system for tumour cell-specific gene delivery using a universal bungarotoxin linker. |
| title | Multi-component polymeric system for tumour cell-specific gene delivery using a universal bungarotoxin linker. |
| title_full | Multi-component polymeric system for tumour cell-specific gene delivery using a universal bungarotoxin linker. |
| title_fullStr | Multi-component polymeric system for tumour cell-specific gene delivery using a universal bungarotoxin linker. |
| title_full_unstemmed | Multi-component polymeric system for tumour cell-specific gene delivery using a universal bungarotoxin linker. |
| title_short | Multi-component polymeric system for tumour cell-specific gene delivery using a universal bungarotoxin linker. |
| title_sort | multi component polymeric system for tumour cell specific gene delivery using a universal bungarotoxin linker |
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