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  1. Article: Biotechnological Evolution of siRNA Molecules: From Bench Tool to the Refined Drug.

    de Brito E Cunha, Danielle / Frederico, Ana Beatriz Teixeira / Azamor, Tamiris / Melgaço, Juliana Gil / da Costa Neves, Patricia Cristina / Bom, Ana Paula Dinis Ano / Tilli, Tatiana Martins / Missailidis, Sotiris

    Pharmaceuticals (Basel, Switzerland)

    2022  Volume 15, Issue 5

    Abstract: The depth and versatility of siRNA technologies enable their use in disease targets that are undruggable by small molecules or that seek to achieve a refined turn-off of the genes for any therapeutic area. Major extracellular barriers are enzymatic ... ...

    Abstract The depth and versatility of siRNA technologies enable their use in disease targets that are undruggable by small molecules or that seek to achieve a refined turn-off of the genes for any therapeutic area. Major extracellular barriers are enzymatic degradation of siRNAs by serum endonucleases and RNAases, renal clearance of the siRNA delivery system, the impermeability of biological membranes for siRNA, activation of the immune system, plasma protein sequestration, and capillary endothelium crossing. To overcome the intrinsic difficulties of the use of siRNA molecules, therapeutic applications require nanometric delivery carriers aiming to protect double-strands and deliver molecules to target cells. This review discusses the history of siRNAs, siRNA design, and delivery strategies, with a focus on progress made regarding siRNA molecules in clinical trials and how siRNA has become a valuable asset for biopharmaceutical companies.
    Language English
    Publishing date 2022-05-05
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2193542-7
    ISSN 1424-8247
    ISSN 1424-8247
    DOI 10.3390/ph15050575
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Intranasal Liposomal Formulation of Spike Protein Adjuvanted with CpG Protects and Boosts Heterologous Immunity of hACE2 Transgenic Mice to SARS-CoV-2 Infection.

    Russo, Momtchilo / Mendes-Corrêa, Maria Cássia / Lins, Bruna B / Kersten, Victor / Pernambuco Filho, Paulo C A / Martins, Toni Ricardo / Tozetto-Mendoza, Tânia Regina / Vilas Boas, Lucy Santos / Gomes, Brisa Moreira / Dati, Livia Mendonça Munhoz / Duarte-Neto, Amaro Nunes / Reigado, Gustavo Roncoli / Frederico, Ana Beatriz T / de Brito E Cunha, Danielle R de A / de Paula, Anderson Vicente / da Silva, José Igor G / Vasconcelos, Carlos F Moreira / Chambergo, Felipe S / Nunes, Viviane Abreu /
    Ano Bom, Ana Paula Dinis / Castilho, Leda R / Martins, Rodrigo A P / Hirata, Mario Hiroyuki / Mirotti, Luciana

    Vaccines

    2023  Volume 11, Issue 11

    Abstract: Mucosal vaccination appears to be suitable to protect against SARS-CoV-2 infection. In this study, we tested an intranasal mucosal vaccine candidate for COVID-19 that consisted of a cationic liposome containing a trimeric SARS-CoV-2 spike protein and CpG- ...

    Abstract Mucosal vaccination appears to be suitable to protect against SARS-CoV-2 infection. In this study, we tested an intranasal mucosal vaccine candidate for COVID-19 that consisted of a cationic liposome containing a trimeric SARS-CoV-2 spike protein and CpG-ODNs, a Toll-like receptor 9 agonist, as an adjuvant. In vitro and in vivo experiments indicated the absence of toxicity following the intranasal administration of this vaccine formulation. First, we found that subcutaneous or intranasal vaccination protected hACE-2 transgenic mice from infection with the wild-type (Wuhan) SARS-CoV-2 strain, as shown by weight loss and mortality indicators. However, when compared with subcutaneous administration, the intranasal route was more effective in the pulmonary clearance of the virus and induced higher neutralizing antibodies and anti-S IgA titers. In addition, the intranasal vaccination afforded protection against gamma, delta, and omicron virus variants of concern. Furthermore, the intranasal vaccine formulation was superior to intramuscular vaccination with a recombinant, replication-deficient chimpanzee adenovirus vector encoding the SARS-CoV-2 spike glycoprotein (Oxford/AstraZeneca) in terms of virus lung clearance and production of neutralizing antibodies in serum and bronchial alveolar lavage (BAL). Finally, the intranasal liposomal formulation boosted heterologous immunity induced by previous intramuscular vaccination with the Oxford/AstraZeneca vaccine, which was more robust than homologous immunity.
    Language English
    Publishing date 2023-11-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2703319-3
    ISSN 2076-393X
    ISSN 2076-393X
    DOI 10.3390/vaccines11111732
    Database MEDical Literature Analysis and Retrieval System OnLINE

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