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Pregled bibliografske jedinice broj: 1071192

Identification of folate receptor α (FRα) binding oligopeptides and their evaluation for targeted virotherapy applications


Hulin-Curtis, Sarah L.; Davies, James A.; Nestić, Davor; Bates, Emily A.; Baker, Alexander T.; Cunliffe, Tabitha G.; Majhen, Dragomira; Chester, John D.; Parker, Alan L.
Identification of folate receptor α (FRα) binding oligopeptides and their evaluation for targeted virotherapy applications // Cancer gene therapy, 1 (2020), s41417-019-0156-0, 14 doi:10.1038/s41417-019-0156-0 (međunarodna recenzija, članak, znanstveni)


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Naslov
Identification of folate receptor α (FRα) binding oligopeptides and their evaluation for targeted virotherapy applications

Autori
Hulin-Curtis, Sarah L. ; Davies, James A. ; Nestić, Davor ; Bates, Emily A. ; Baker, Alexander T. ; Cunliffe, Tabitha G. ; Majhen, Dragomira ; Chester, John D. ; Parker, Alan L.

Izvornik
Cancer gene therapy (0929-1903) 1 (2020); S41417-019-0156-0, 14

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Oncolytic virotherapies ; mediated gene delivery ; phage display ; adenovirus vector ; ovarian-cancer ; in-vivo ; hi loop ; peptide ; ligands ; blood ; cells

Sažetak
Oncolytic virotherapies (OV) based on human adenoviral (HAdV) vectors hold significant promise for the treatment of advanced ovarian cancers where local, intraperitoneal delivery to tumour metastases is feasible, bypassing many complexities associated with intravascular delivery. The efficacy of HAdV-C5-based OV is hampered by a lack of tumour selectivity, where the primary receptor, hCAR, is commonly downregulated during malignant transformation. Conversely, folate receptor alpha (FRα) is highly expressed on ovarian cancer cells, providing a compelling target for tumour selective delivery of virotherapies. Here, we identify high-affinity FRα-binding oligopeptides for genetic incorporation into HAdV-C5 vectors. Biopanning identified a 12-mer linear peptide, DWSSWVYRDPQT, and two 7-mer cysteine-constrained peptides, CIGNSNTLC and CTVRTSAEC that bound FRα in the context of the phage particle. Synthesised lead peptide, CTVRTSAEC, bound specifically to FRα and could be competitively inhibited with folic acid. To assess the capacity of the elucidated FRα- binding oligopeptides to target OV to FRα, we genetically incorporated the peptides into the HAdV-C5 fiber-knob HI loop including in vectors genetically ablated for hCAR interactions. Unfortunately, the recombinant vectors failed to efficiently target transduction via FRα due to defective intracellular trafficking following entry via FRα, indicating that whilst the peptides identified may have potential for applications for targeted drug delivery, they require additional refinement for targeted virotherapy applications.

Izvorni jezik
Engleski

Znanstvena područja
Biologija



POVEZANOST RADA


Ustanove
Institut "Ruđer Bošković", Zagreb

Profili:

Avatar Url Dragomira Majhen (autor)

Avatar Url Davor Nestić (autor)

Citiraj ovu publikaciju

Hulin-Curtis, Sarah L.; Davies, James A.; Nestić, Davor; Bates, Emily A.; Baker, Alexander T.; Cunliffe, Tabitha G.; Majhen, Dragomira; Chester, John D.; Parker, Alan L.
Identification of folate receptor α (FRα) binding oligopeptides and their evaluation for targeted virotherapy applications // Cancer gene therapy, 1 (2020), s41417-019-0156-0, 14 doi:10.1038/s41417-019-0156-0 (međunarodna recenzija, članak, znanstveni)
Hulin-Curtis, S., Davies, J., Nestić, D., Bates, E., Baker, A., Cunliffe, T., Majhen, D., Chester, J. & Parker, A. (2020) Identification of folate receptor α (FRα) binding oligopeptides and their evaluation for targeted virotherapy applications. Cancer gene therapy, 1, s41417-019-0156-0, 14 doi:10.1038/s41417-019-0156-0.
@article{article, year = {2020}, pages = {14}, DOI = {10.1038/s41417-019-0156-0}, chapter = {s41417-019-0156-0}, keywords = {Oncolytic virotherapies, mediated gene delivery, phage display, adenovirus vector, ovarian-cancer, in-vivo, hi loop, peptide, ligands, blood, cells}, journal = {Cancer gene therapy}, doi = {10.1038/s41417-019-0156-0}, volume = {1}, issn = {0929-1903}, title = {Identification of folate receptor α (FRα) binding oligopeptides and their evaluation for targeted virotherapy applications}, keyword = {Oncolytic virotherapies, mediated gene delivery, phage display, adenovirus vector, ovarian-cancer, in-vivo, hi loop, peptide, ligands, blood, cells}, chapternumber = {s41417-019-0156-0} }

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


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