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  1. Article ; Online: Pseudotyping Bacteriophage P2 Tail Fibers to Extend the Host Range for Biomedical Applications.

    Cunliffe, Tabitha G / Parker, Alan L / Jaramillo, Alfonso

    ACS synthetic biology

    2022  Volume 11, Issue 10, Page(s) 3207–3215

    Abstract: Bacteriophages (phages) represent powerful potential treatments against antibiotic-resistant bacterial infections. Antibiotic-resistant bacteria represent a significant threat to global health, with an estimated 70% of infection-causing bacteria being ... ...

    Abstract Bacteriophages (phages) represent powerful potential treatments against antibiotic-resistant bacterial infections. Antibiotic-resistant bacteria represent a significant threat to global health, with an estimated 70% of infection-causing bacteria being resistant to one or more antibiotics. Developing novel antibiotics against the limited number of cellular targets is expensive and time-consuming, and bacteria can rapidly develop resistance. While bacterial resistance to phage can evolve, bacterial resistance to phage does not appear to spread through lateral gene transfer, and phage may similarly adapt through mutation to recover infectivity. Phages have been identified for all known bacteria, allowing the strain-selective killing of pathogenic bacteria. Here, we re-engineered the
    MeSH term(s) Host Specificity ; Bacteriophage P2 ; Lipopolysaccharides ; Proteome ; Bacteriophages/genetics ; Anti-Bacterial Agents
    Chemical Substances Lipopolysaccharides ; Proteome ; Anti-Bacterial Agents
    Language English
    Publishing date 2022-09-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2161-5063
    ISSN (online) 2161-5063
    DOI 10.1021/acssynbio.1c00629
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Hitting the Target but Missing the Point: Recent Progress towards Adenovirus-Based Precision Virotherapies.

    Cunliffe, Tabitha G / Bates, Emily A / Parker, Alan L

    Cancers

    2020  Volume 12, Issue 11

    Abstract: More people are surviving longer with cancer. Whilst this can be partially attributed to advances in early detection of cancers, there is little doubt that the improvement in survival statistics is also due to the expansion in the spectrum of treatments ... ...

    Abstract More people are surviving longer with cancer. Whilst this can be partially attributed to advances in early detection of cancers, there is little doubt that the improvement in survival statistics is also due to the expansion in the spectrum of treatments available for efficacious treatment. Transformative amongst those are immunotherapies, which have proven effective agents for treating immunogenic forms of cancer, although immunologically "cold" tumour types remain refractive. Oncolytic viruses, such as those based on adenovirus, have great potential as anti-cancer agents and have seen a resurgence of interest in recent years. Amongst their many advantages is their ability to induce immunogenic cell death (ICD) of infected tumour cells, thus providing the alluring potential to synergise with immunotherapies by turning immunologically "cold" tumours "hot". Additionally, enhanced immune mediated cell killing can be promoted through the local overexpression of immunological transgenes, encoded from within the engineered viral genome. To achieve this full potential requires the development of refined, tumour selective "precision virotherapies" that are extensively engineered to prevent off-target up take via native routes of infection and targeted to infect and replicate uniquely within malignantly transformed cells. Here, we review the latest advances towards this holy grail within the adenoviral field.
    Language English
    Publishing date 2020-11-11
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers12113327
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Broad sialic acid usage amongst species D human adenovirus.

    Mundy, Rosie M / Baker, Alexander T / Bates, Emily A / Cunliffe, Tabitha G / Teijeira-Crespo, Alicia / Moses, Elise / Rizkallah, Pierre J / Parker, Alan L

    Npj viruses

    2023  Volume 1, Issue 1, Page(s) 1

    Abstract: Human adenoviruses (HAdV) are widespread pathogens causing usually mild infections. The Species D (HAdV-D) cause gastrointestinal tract infections and epidemic keratoconjunctivitis (EKC). Despite being significant pathogens, knowledge around HAdV-D ... ...

    Abstract Human adenoviruses (HAdV) are widespread pathogens causing usually mild infections. The Species D (HAdV-D) cause gastrointestinal tract infections and epidemic keratoconjunctivitis (EKC). Despite being significant pathogens, knowledge around HAdV-D mechanism of cell infection is lacking. Sialic acid (SA) usage has been proposed as a cell infection mechanism for EKC causing HAdV-D. Here we highlight an important role for SA engagement by many HAdV-D. We provide apo state crystal structures of 7 previously undetermined HAdV-D fiber-knob proteins, and structures of HAdV-D25, D29, D30 and D53 fiber-knob proteins in complex with SA. Biologically, we demonstrate that removal of cell surface SA reduced infectivity of HAdV-C5 vectors pseudotyped with HAdV-D fiber-knob proteins, whilst engagement of the classical HAdV receptor CAR was variable. Our data indicates variable usage of SA and CAR across HAdV-D. Better defining these interactions will enable improved development of antivirals and engineering of the viruses into refined therapeutic vectors.
    Language English
    Publishing date 2023-09-26
    Publishing country England
    Document type Journal Article
    ISSN 2948-1767
    ISSN (online) 2948-1767
    DOI 10.1038/s44298-023-00001-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Development of a low-seroprevalence, αvβ6 integrin-selective virotherapy based on human adenovirus type 10.

    Bates, Emily A / Davies, James A / Váňová, Jana / Nestić, Davor / Meniel, Valerie S / Koushyar, Sarah / Cunliffe, Tabitha G / Mundy, Rosie M / Moses, Elise / Uusi-Kerttula, Hanni K / Baker, Alexander T / Cole, David K / Majhen, Dragomira / Rizkallah, Pierre J / Phesse, Toby / Chester, John D / Parker, Alan L

    Molecular therapy oncolytics

    2022  Volume 25, Page(s) 43–56

    Abstract: Oncolytic virotherapies (OV) hold immense clinical potential. OV based on human adenoviruses (HAdV) derived from HAdV with naturally low rates of pre-existing immunity will be beneficial for future clinical translation. We generated a low-seroprevalence ... ...

    Abstract Oncolytic virotherapies (OV) hold immense clinical potential. OV based on human adenoviruses (HAdV) derived from HAdV with naturally low rates of pre-existing immunity will be beneficial for future clinical translation. We generated a low-seroprevalence HAdV-D10 serotype vector incorporating an αvβ6 integrin-selective peptide, A20, to target αvβ6-positive tumor cell types. HAdV-D10 has limited natural tropism. Structural and biological studies of HAdV-D10 knob protein highlighted low-affinity engagement with native adenoviral receptors CAR and sialic acid. HAdV-D10 fails to engage blood coagulation factor X, potentially eliminating "off-target" hepatic sequestration
    Language English
    Publishing date 2022-03-16
    Publishing country United States
    Document type Journal Article
    ISSN 2372-7705
    ISSN 2372-7705
    DOI 10.1016/j.omto.2022.03.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: 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

    Cancer gene therapy

    2020  Volume 27, Issue 10-11, Page(s) 785–798

    Abstract: 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 ... ...

    Abstract 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.
    MeSH term(s) Animals ; Female ; Folate Receptor 1/metabolism ; Genetic Engineering/methods ; Humans ; Mice ; Mice, Nude ; Oligopeptides/metabolism ; Oncolytic Virotherapy/methods
    Chemical Substances Folate Receptor 1 ; Oligopeptides
    Language English
    Publishing date 2020-01-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1212513-1
    ISSN 1476-5500 ; 0929-1903
    ISSN (online) 1476-5500
    ISSN 0929-1903
    DOI 10.1038/s41417-019-0156-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Complete Genome Sequence of Peste des Petits Ruminants Virus from Georgia, 2016.

    Rajko-Nenow, Paulina Z / Cunliffe, Tabitha G / Flannery, John T / Ropiak, Honorata M / Avaliani, Lasha / Donduashvili, Marina / Baron, Michael D / Batten, Carrie A

    Genome announcements

    2017  Volume 5, Issue 41

    Abstract: We report here the complete genome sequence of a peste des petits ruminants virus (PPRV) from the first outbreak of the disease in Georgia in January 2016. Genome sequencing was performed using Illumina next-generation sequencing technology in ... ...

    Abstract We report here the complete genome sequence of a peste des petits ruminants virus (PPRV) from the first outbreak of the disease in Georgia in January 2016. Genome sequencing was performed using Illumina next-generation sequencing technology in conjunction with Sanger sequencing. This PPRV/Georgia/Tbilisi/2016 genome sequence clustered within lineage IV PPRV viruses.
    Language English
    Publishing date 2017-10-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2704277-7
    ISSN 2169-8287
    ISSN 2169-8287
    DOI 10.1128/genomeA.01091-17
    Database MEDical Literature Analysis and Retrieval System OnLINE

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