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>
firstname.lastname@example.org | TechnologieAllianz e.V.
Flexible and rigid, heavy-metal free organic redox polymer batteries
09.03.2017 | TechnologieAllianz e.V.
Quat primer polymers the universal key to permanent surface functionalization
27.02.2017 | TechnologieAllianz e.V.
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
27.03.2017 | Earth Sciences
27.03.2017 | Life Sciences
27.03.2017 | Life Sciences