idw – Informationsdienst Wissenschaft

Nachrichten, Termine, Experten

Grafik: idw-Logo
Thema Corona

Imagefilm
Science Video Project
idw-News App:

AppStore



Teilen: 
13.10.2021 14:30

New Gene Shuttles for Targeted Gene Transfer into Mouse T Lymphocytes

Dr. Susanne Stöcker Presse, Informationen
Paul-Ehrlich-Institut - Bundesinstitut für Impfstoffe und biomedizinische Arzneimittel

    Scientists at the Paul-Ehrlich-Institut (PEI) have discovered two new ways of effectively transferring genes into mouse cytotoxic T lymphocytes (CTL) using viral gene shuttles. CTL are members of the white blood cell family and are also known as killer cells. The new tools have the potential to facilitate preclinical studies for gene therapies in the immunotherapeutic field. In addition, the work also has broader relevance for gene therapy: it describes a new class of viral gene ferries, called DART-AAV, which enables gene transfer with unprecedented cell type-precision.

    Gene therapies insert genetic information into patients' cells to achieve a therapeutic benefit. Therapeutic genes are introduced into cells, where they compensate for previously impaired functions or perform new functions, such as recognizing tumor cells. Approved gene therapies, for example for the treatment of advanced hematological cancers or spinal muscular atrophy, are already showing very good efficacy in practice.

    There are various methods for gene transfer. Viral vectors are frequently used. These are modified, non-replicating viruses, also known as gene shuttles or viral vectors. These gene shuttles are often based on lentiviruses or adeno-associated viruses (AAV). Because of their non-integrative nature, the latter are often used when transient genetic modification or modification of non-dividing somatic cells is required.

    Suitable animal models are of great importance for the preclinical development of new gene therapies. The introduction of genes into white blood cells (lymphocytes) of mice has so far been a major technical challenge due to low efficiency and a lack of cell type specificity. The team led by Professor Dr Christian Buchholz, head of the research group Molecular Biotechnology and Gene Therapy at the Paul-Ehrlich-Institut, took up this challenge. The scientists focused on CTL, which carry the cell surface marker CD8.

    CTL can selectively destroy body cells that have, for example, been infected with a pathogen or have degenerated into cancer cells. Since CTL play a crucial role in the immune system, there is a great need for gene shuttles that enable efficient gene delivery into this cell type.

    The researchers' working hypothesis was that efficient gene transfer into CTL can be achieved by targeting lentiviral and adeno-associated vectors to the CD8 surface marker.

    To this end, the researchers generated so-called designed ankyrin repeat proteins (DARPins) that bind the CD8 molecule of mice. The viral vector carries CD8-binding DARPins on its surface and attaches to the target cell by binding to CD8. The resulting novel gene shuttles are able to selectively modify mouse CTL with an efficiency not previously observed. This was particularly surprising for the AAV-based gene shuttles, as conventional AAVs were barely able to transfer genes into mouse CTL. The newly developed gene shuttles are highly specific for mouse CTL, achieving selectivities of more than 99%. The significance of this discovery extends beyond this cell type, as the cell type specificity of the gene shuttles can be changed by replacing the ankyrin repeat protein. The new class of AAV gene shuttles is now referred to as DART (DARPin-targeted)-AAV.

    Using CD8-binding DARPins, highly specific and efficient vectors for targeted gene transfer into mouse CTL were generated. Professor Dr Buchholz concludes: ""The efficiency of the new tools surprised us. They could therefore represent an important milestone for the development of future gene therapies in the immunotherapeutic field.""


    Originalpublikation:

    Michels A, Frank AM, Günther DM, Mataei M, Börner K, Grimm D, Hartmann J, Buchholz CJ (2021): Lentiviral and adeno-associated vectors efficiently transduce mouse T lymphocytes when targeted to murine CD8.
    Mol Ther Methods Clin Oct 1 [Epub ahead of print].
    DOI: 10.1016/j.omtm.2021.09.014


    Weitere Informationen:

    https://www.sciencedirect.com/science/article/pii/S2329050121001522?via%3Dihub - Abstraqct
    https://www.pei.de/EN/newsroom/press-releases/year/2021/20-new-gene-shuttles-for... - This press release on the Website of the Paul-Ehrlich-Institut


    Merkmale dieser Pressemitteilung:
    Journalisten, Wissenschaftler
    Biologie, Medizin
    überregional
    Forschungsergebnisse, Wissenschaftliche Publikationen
    Englisch


    Hilfe

    Die Suche / Erweiterte Suche im idw-Archiv
    Verknüpfungen

    Sie können Suchbegriffe mit und, oder und / oder nicht verknüpfen, z. B. Philo nicht logie.

    Klammern

    Verknüpfungen können Sie mit Klammern voneinander trennen, z. B. (Philo nicht logie) oder (Psycho und logie).

    Wortgruppen

    Zusammenhängende Worte werden als Wortgruppe gesucht, wenn Sie sie in Anführungsstriche setzen, z. B. „Bundesrepublik Deutschland“.

    Auswahlkriterien

    Die Erweiterte Suche können Sie auch nutzen, ohne Suchbegriffe einzugeben. Sie orientiert sich dann an den Kriterien, die Sie ausgewählt haben (z. B. nach dem Land oder dem Sachgebiet).

    Haben Sie in einer Kategorie kein Kriterium ausgewählt, wird die gesamte Kategorie durchsucht (z.B. alle Sachgebiete oder alle Länder).