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  1. Article ; Online: Nickel import and export in the human pathogen Helicobacter pylori, perspectives from molecular modelling.

    Camporesi, Giulia / Minzoni, Arianna / Morasso, Luca / Ciurli, Stefano / Musiani, Francesco

    Metallomics : integrated biometal science

    2021  Volume 13, Issue 12

    Abstract: The uptake of essential metal ions and the ability to extrude them when their excess causes toxicity are crucial processes for all living beings. Nickel is a virulence factor for several human pathogens and in particular for the human gastric pathogen ... ...

    Abstract The uptake of essential metal ions and the ability to extrude them when their excess causes toxicity are crucial processes for all living beings. Nickel is a virulence factor for several human pathogens and in particular for the human gastric pathogen Helicobacter pylori because of its crucial role in the catalytic activity of two Ni-dependent enzymes, urease and hydrogenase. H. pylori requires efficient uptake mechanisms to import Ni(II) because of its scarcity in the human body, but the molecular details of Ni(II) homeostasis are not fully known. Here we offer a structural framework for the machinery of Ni(II) import/export in H. pylori, obtained through comparative modelling and macromolecular docking. The model structures reported in this perspective are initial steps towards the understanding of these processes at the molecular level and in the direction to exploit them to eradicate infections caused by this family of pathogens. The differences between the structural models obtained by using both the recently released neural network-based approach implemented in AlphaFold2 and a more classical user-driven modelling procedure are also discussed.
    MeSH term(s) Biological Transport ; Helicobacter pylori/metabolism ; Helicobacter pylori/pathogenicity ; Models, Molecular ; Nickel/metabolism ; Virulence Factors
    Chemical Substances Virulence Factors ; Nickel (7OV03QG267)
    Language English
    Publishing date 2021-11-17
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2474317-3
    ISSN 1756-591X ; 1756-5901
    ISSN (online) 1756-591X
    ISSN 1756-5901
    DOI 10.1093/mtomcs/mfab066
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The downstream bioprocess toolbox for therapeutic viral vectors

    Kilgore, Ryan / Minzoni, Arianna / Shastry, Shriarjun / Smith, Will / Barbieri, Eduardo / Wu, Yuxuan / LeBarre, Jacob P. / Chu, Wenning / O'Brien, Juliana / Menegatti, Stefano

    Journal of Chromatography A. 2023 Oct., v. 1709 p.464337-

    2023  

    Abstract: Viral vectors are poised to acquire a prominent position in modern medicine and biotechnology owing to their role as delivery agents for gene therapies, oncolytic agents, vaccine platforms, and a gateway to engineer cell therapies as well as plants and ... ...

    Abstract Viral vectors are poised to acquire a prominent position in modern medicine and biotechnology owing to their role as delivery agents for gene therapies, oncolytic agents, vaccine platforms, and a gateway to engineer cell therapies as well as plants and animals for sustainable agriculture. The success of viral vectors will critically depend on the availability of flexible and affordable biomanufacturing strategies that can meet the growing demand by clinics and biotech companies worldwide. In this context, a key role will be played by downstream process technology: while initially adapted from protein purification media, the purification toolbox for viral vectors is currently undergoing a rapid expansion to fit the unique biomolecular characteristics of these products. Innovation efforts are articulated on two fronts, namely (i) the discovery of affinity ligands that target adeno-associated virus, lentivirus, adenovirus, etc.; (ii) the development of adsorbents with innovative morphologies, such as membranes and 3D printed monoliths, that fit the size of viral vectors. Complementing these efforts are the design of novel process layouts that capitalize on novel ligands and adsorbents to ensure high yield and purity of the product while safeguarding its therapeutic efficacy and safety; and a growing panel of analytical methods that monitor the complex array of critical quality attributes of viral vectors and correlate them to the purification strategies. To help explore this complex and evolving environment, this study presents a comprehensive overview of the downstream bioprocess toolbox for viral vectors established in the last decade, and discusses present efforts and future directions contributing to the success of this promising class of biological medicines.
    Keywords Adenoviridae ; Dependoparvovirus ; Lentivirus ; adsorbents ; bioprocessing ; biotechnology ; chromatography ; genes ; ligands ; medicine ; sustainable agriculture ; therapeutics ; three-dimensional printing ; vaccines ; Viral vectors ; Gene therapy ; Affinity ligands ; AAV
    Language English
    Dates of publication 2023-10
    Publishing place Elsevier B.V.
    Document type Article ; Online
    ZDB-ID 218139-3
    ISSN 0021-9673 ; 0378-4355 ; 0376-737X
    ISSN 0021-9673 ; 0378-4355 ; 0376-737X
    DOI 10.1016/j.chroma.2023.464337
    Database NAL-Catalogue (AGRICOLA)

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  3. Article ; Online: The downstream bioprocess toolbox for therapeutic viral vectors.

    Kilgore, Ryan / Minzoni, Arianna / Shastry, Shriarjun / Smith, Will / Barbieri, Eduardo / Wu, Yuxuan / LeBarre, Jacob P / Chu, Wenning / O'Brien, Juliana / Menegatti, Stefano

    Journal of chromatography. A

    2023  Volume 1709, Page(s) 464337

    Abstract: Viral vectors are poised to acquire a prominent position in modern medicine and biotechnology owing to their role as delivery agents for gene therapies, oncolytic agents, vaccine platforms, and a gateway to engineer cell therapies as well as plants and ... ...

    Abstract Viral vectors are poised to acquire a prominent position in modern medicine and biotechnology owing to their role as delivery agents for gene therapies, oncolytic agents, vaccine platforms, and a gateway to engineer cell therapies as well as plants and animals for sustainable agriculture. The success of viral vectors will critically depend on the availability of flexible and affordable biomanufacturing strategies that can meet the growing demand by clinics and biotech companies worldwide. In this context, a key role will be played by downstream process technology: while initially adapted from protein purification media, the purification toolbox for viral vectors is currently undergoing a rapid expansion to fit the unique biomolecular characteristics of these products. Innovation efforts are articulated on two fronts, namely (i) the discovery of affinity ligands that target adeno-associated virus, lentivirus, adenovirus, etc.; (ii) the development of adsorbents with innovative morphologies, such as membranes and 3D printed monoliths, that fit the size of viral vectors. Complementing these efforts are the design of novel process layouts that capitalize on novel ligands and adsorbents to ensure high yield and purity of the product while safeguarding its therapeutic efficacy and safety; and a growing panel of analytical methods that monitor the complex array of critical quality attributes of viral vectors and correlate them to the purification strategies. To help explore this complex and evolving environment, this study presents a comprehensive overview of the downstream bioprocess toolbox for viral vectors established in the last decade, and discusses present efforts and future directions contributing to the success of this promising class of biological medicines.
    Language English
    Publishing date 2023-09-09
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1171488-8
    ISSN 1873-3778 ; 0021-9673
    ISSN (online) 1873-3778
    ISSN 0021-9673
    DOI 10.1016/j.chroma.2023.464337
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Rational design and experimental evaluation of peptide ligands for the purification of adeno-associated viruses via affinity chromatography.

    Shastry, Shriarjun / Chu, Wenning / Barbieri, Eduardo / Greback-Clarke, Paul / Smith, William K / Cummings, Christopher / Minzoni, Arianna / Pancorbo, Jennifer / Gilleskie, Gary / Ritola, Kimberly / Daniele, Michael A / Johnson, Thomas F / Menegatti, Stefano

    Biotechnology journal

    2023  Volume 19, Issue 1, Page(s) e2300230

    Abstract: Adeno-associated viruses (AAVs) have acquired a central role in modern medicine as delivery agents for gene therapies targeting rare diseases. While new AAVs with improved tissue targeting, potency, and safety are being introduced, their biomanufacturing ...

    Abstract Adeno-associated viruses (AAVs) have acquired a central role in modern medicine as delivery agents for gene therapies targeting rare diseases. While new AAVs with improved tissue targeting, potency, and safety are being introduced, their biomanufacturing technology is lagging. In particular, the AAV purification pipeline hinges on protein ligands for the affinity-based capture step. While featuring excellent AAV binding capacity and selectivity, these ligands require strong acid (pH <3) elution conditions, which can compromise the product's activity and stability. Additionally, their high cost and limited lifetime has a significant impact on the price tag of AAV-based therapies. Seeking to introduce a more robust and affordable affinity technology, this study introduces a cohort of peptide ligands that (i) mimic the biorecognition activity of the AAV receptor (AAVR) and anti-AAV antibody A20, (ii) enable product elution under near-physiological conditions (pH 6.0), and (iii) grant extended reusability by withstanding multiple regenerations. A20-mimetic CYIHFSGYTNYNPSLKSC and AAVR-mimetic CVIDGSQSTDDDKIC demonstrated excellent capture of serotypes belonging to distinct clones/clades - namely, AAV1, AAV2, AAV5, AAV6, AAV8, and AAV9. This corroborates the in silico models documenting their ability to target regions of the viral capsid that are conserved across all serotypes. CVIDGSQSTDDDKIC-Toyopearl resin features binding capacity (≈10
    MeSH term(s) Humans ; Dependovirus/genetics ; Capsid/chemistry ; HEK293 Cells ; Transduction, Genetic ; Peptides/metabolism ; Ligands ; Chromatography, Affinity ; Genetic Vectors/genetics
    Chemical Substances Peptides ; Ligands
    Language English
    Publishing date 2023-09-28
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2221885-3
    ISSN 1860-7314 ; 1860-6768
    ISSN (online) 1860-7314
    ISSN 1860-6768
    DOI 10.1002/biot.202300230
    Database MEDical Literature Analysis and Retrieval System OnLINE

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