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.
Dosing system of bulk material (granulates) for expansion injection molding
19.01.2017 | TechnologieAllianz e.V.
Efficient method for Chain Multiplication of unsaturated fatty acids - synthesis of ultra long-chain compounds
18.01.2017 | TechnologieAllianz e.V.
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
20.01.2017 | Life Sciences
20.01.2017 | Physics and Astronomy
20.01.2017 | Materials Sciences