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  1. Article: Selective Delivery to Cardiac Muscle Cells Using Cell-Specific Aptamers.

    Philippou, Styliana / Mastroyiannopoulos, Nikolaos P / Tomazou, Marios / Oulas, Anastasios / Ackers-Johnson, Matthew / Foo, Roger S / Spyrou, George M / Phylactou, Leonidas A

    Pharmaceuticals (Basel, Switzerland)

    2023  Volume 16, Issue 9

    Abstract: In vivo SELEX is an advanced adaptation of Systematic Evolution of Ligands by Exponential Enrichment (SELEX) that allows the development of aptamers capable of recognizing targets directly within their natural microenvironment. While this methodology ... ...

    Abstract In vivo SELEX is an advanced adaptation of Systematic Evolution of Ligands by Exponential Enrichment (SELEX) that allows the development of aptamers capable of recognizing targets directly within their natural microenvironment. While this methodology ensures a higher translation potential for the selected aptamer, it does not select for aptamers that recognize specific cell types within a tissue. Such aptamers could potentially improve the development of drugs for several diseases, including neuromuscular disorders, by targeting solely the proteins involved in their pathogenesis. Here, we describe our attempt to utilize in vivo SELEX with a modification in the methodology that drives the selection of intravenously injected aptamers towards a specific cell type of interest. Our data suggest that the incorporation of a cell enrichment step can direct the in vivo localization of RNA aptamers into cardiomyocytes, the cardiac muscle cells, more readily over other cardiac cells. Given the crucial role of cardiomyocytes in the disease pathology in DMD cardiomyopathy and therapy, these aptamers hold great potential as drug delivery vehicles with cardiomyocyte selectivity.
    Language English
    Publishing date 2023-09-06
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2193542-7
    ISSN 1424-8247
    ISSN 1424-8247
    DOI 10.3390/ph16091264
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Selection and Identification of Skeletal-Muscle-Targeted RNA Aptamers.

    Philippou, Styliana / Mastroyiannopoulos, Nikolaos P / Makrides, Neoklis / Lederer, Carsten W / Kleanthous, Marina / Phylactou, Leonidas A

    Molecular therapy. Nucleic acids

    2017  Volume 10, Page(s) 199–214

    Abstract: Oligonucleotide gene therapy has shown great promise for the treatment of muscular dystrophies. Nevertheless, the selective delivery to affected muscles has shown to be challenging because of their high representation in the body and the high complexity ... ...

    Abstract Oligonucleotide gene therapy has shown great promise for the treatment of muscular dystrophies. Nevertheless, the selective delivery to affected muscles has shown to be challenging because of their high representation in the body and the high complexity of their cell membranes. Current trials show loss of therapeutic molecules to non-target tissues leading to lower target efficacy. Therefore, strategies that increase uptake efficiency would be particularly compelling. To address this need, we applied a cell-internalization SELEX (Systematic Evolution of Ligands by Exponential Enrichment) approach and identified a skeletal muscle-specific RNA aptamer. A01B RNA aptamer preferentially internalizes in skeletal muscle cells and exhibits decreased affinity for off-target cells. Moreover, this in vitro selected aptamer retained its functionality in vivo, suggesting a potential new approach for targeting skeletal muscles. Ultimately, this will aid in the development of targeted oligonucleotide therapies against muscular dystrophies.
    Language English
    Publishing date 2017-12-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2662631-7
    ISSN 2162-2531
    ISSN 2162-2531
    DOI 10.1016/j.omtn.2017.12.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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