MicroRNA206 target Site for Prevention of Unwan-ted Transgene Expression in Skeletal Muscle

</a><strong>Background</strong><br>

Adeno-associated virus (AAV) vectors, in particular serotype AAV9, are the most potent and promising vector types used for gene transfer into the heart. However AAV vectors also transduce non-target organs such as liver or skeletal muscle. Reduction of AAV-mediated transgene expression in non-target organs is an important aim to reduce or avoid unwanted side effects in gene therapy. The use of heart-specific promoters or the use of non-target organ specific microRNAs (miRNA) and its specific target site are approaches to control transgene transcription. E.g. the use of a miR-122 target site in the 3´UTR of an AAV9 vector leads to silencing of the transgene expression in the non-target organ liver (miR-122 is a liver-specific microRNA) (Geisler et al. 2011). <br><br> <strong>Technology</strong><br> We offer a mutated miR-206 target site (TS) as a control element for the si-lencing of unwanted transgene expression in the non-target organ skeletal muscle while allowing transgene expression in the target organ (e.g. heart). miR-206 is highly expressed in skeletal muscle and virtually absent in the heart. Unexpectedly, the expression of wild-type miR-206TS in the AAV9 transgene vector indeed exhibited reduced expression of the transgene in skeletal muscle however transgene expression was also silenced in the heart. This was due to the presence of miR-1 in the heart which shows 86% homology to miR-206. Thus miR-1 in the heart also binds to miR-206TS in the AAV9 vector which results in silencing of transgene expression in the heart. The use of specifically mutated miR-206TS overcomes this problem: miR-206 binds furthermore and even better to the mutated miR-206TS whereas miR-1 cannot bind the mutated miR-206TS. Hence, transgene expression is repressed in the skeletal muscle whereas it remains high in the heart.<br><br> <b>Benefits:</b><ul> <li>Enhanced inhibiton of transgene expression in non-target organ skeletal muscle compared to using wild-type miR-206TS</li> <li>Well transgene (hS100A1) expression in the heart of mice injected with an AAV9 vector containing mutated miR206TS and miR-122TS </li></ul> <p><strong>IP Rights</strong><br> US patent application (04/2012) <br><br> <strong>Patent Owner</strong><br> Charité – Universitätsmedizin Berlin Technische Universität Berlin

Weitere Informationen: PDF

ipal GmbH
Tel.: +49 (0)30/2125-4820

Ansprechpartner
Dr. Dirk Dantz

Media Contact

info@technologieallianz.de TechnologieAllianz e.V.

Alle Nachrichten aus der Kategorie: Technologieangebote

Zurück zur Startseite

Kommentare (0)

Schreiben Sie einen Kommentar

Neueste Beiträge

Neues topologisches Metamaterial

… verstärkt Schallwellen exponentiell. Wissenschaftlerinnen und Wissenschaftler am niederländischen Forschungsinstitut AMOLF haben in einer internationalen Kollaboration ein neuartiges Metamaterial entwickelt, durch das sich Schallwellen auf völlig neue Art und Weise…

Astronomen entdecken starke Magnetfelder

… am Rand des zentralen schwarzen Lochs der Milchstraße. Ein neues Bild des Event Horizon Telescope (EHT) hat starke und geordnete Magnetfelder aufgespürt, die vom Rand des supermassereichen schwarzen Lochs…

Faktor für die Gehirnexpansion beim Menschen

Was unterscheidet uns Menschen von anderen Lebewesen? Der Schlüssel liegt im Neokortex, der äußeren Schicht des Gehirns. Diese Gehirnregion ermöglicht uns abstraktes Denken, Kunst und komplexe Sprache. Ein internationales Forschungsteam…

Partner & Förderer