Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Accessing DNA in the cell's powerhouse to treat disease

11.07.2017

A new molecule that reads mitochondrial DNA could pave the way to treat some genetic nerve and muscle diseases

For the first time, a synthetic compound has been made that can bind to DNA in the cells' energy powerhouses, suppressing a gene associated with nerve and muscle disease.


This is a schematic illustration of a mitochondria-specific DNA-based synthetic ligand, called MITO-PIPs that selectively read a target DNA sequence and alter gene transcription.

Credit: Kyoto University iCeMS

Pyrrole-imidazole polyamides (PIPs) are compounds that can read specific DNA sequences inside living cells and silence disease-causing genes. They prevent proteins, called transcription factors, from binding to specific parts of the DNA strand, thus suppressing the transcription of DNA into RNA.

Most DNA is found in the nucleus. But mitochondria, the cell's powerhouses, also host a small amount of DNA. PIPs are capable of crossing the nuclear membrane to bind to nuclear DNA, but are incapable of crossing the mitochondrial membrane.

A team, led by Ganesh Pandian Namasivayam, from Kyoto University's Institute for Integrated Cell-Material Science (iCeMS) succeeded to re-direct PIP to cross the mitochondrial membrane so that it can access its DNA and alter gene transcription.

They achieved this complex feat by complementing PIP with a 'mitochondria-penetrating peptide' (MPP), which is capable of overcoming the mitochondria's energy barrier. The MPP-conjugated PIP called MITO-PIP was designed to block a specific binding site for mitochondrial transcription factor A (TFAM). TFAM is essential in governing mitochondrial metabolism and energy synthesis, playing a role in the transcription of a gene called ND6, says Takuya Hidaka, the first author of the study.

The team found that a TFAM-inhibiting MITO-PIP selectively read a mitochondrial DNA sequence and caused a 60% to 90% reduction in the expression of ND6, depending upon the concentration used. The team then labeled the MITO-PIPs with a molecule that fluoresces when exposed to light and, using special microscopes, confirmed that they localized inside the mitochondria without being present in the nuclei of treated cells.

ND6 is associated with several mitochondrial disorders, including Leber's hereditary optic neuropathy, which causes loss of central vision, mitochondrial myopathy, muscle weakness, seizures and learning difficulties. Hence, chemical control over such disease-associated genes has clinical potential in mitochondrial gene therapy. "We plan to develop an advanced version of MITO-PIPs that can identify and localize only inside diseased mitochondria," says Ganesh.

"Our proof-of-concept study provides a fresh platform that opens new avenues for DNA-based functional ligands that are capable of altering the mitochondrial genome in a sequence-specific manner," concludes the principal investigator Hiroshi Sugiyama. The study was published in the Journal of the American Chemical Society.

###

The paper "Creation of a Synthetic Ligand for Mitochondrial DNA Sequence Recognition and Promoter-Specific Transcription Suppression" appeared on June 16, 2017 in Journal of the American Chemical Society, with doi: 10.1021/jacs.7b05230.

The Institute for Integrated Cell-Material Sciences (iCeMS) at Kyoto University in Japan aims to advance the integration of cell and material sciences, both traditionally strong fields at the university, in a uniquely innovative global research environment. iCeMS combines the biosciences, chemistry, materials science and physics to create materials for mesoscopic cell control and cell-inspired materials. Such developments hold promise for significant advances in medicine, pharmaceutical studies, the environment and industry. http://www.icems.kyoto-u.ac.jp

For information on the research:

Dr. Ganesh Pandian Namasivayam
Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University Institute for Advanced Study
E-mail: ganesh@kuchem.kyoto-u.ac.jp

For information on iCeMS:

Ms. Izumi Mindy Takamiya, Public Relations Officer
Kyoto University Institute for Advanced Study
Phone: 81-75-753-9755

http://www.kyoto-u.ac.jp/en 

Izumi Mindy Takamiya | EurekAlert!

More articles from Life Sciences:

nachricht Closing in on advanced prostate cancer
13.12.2017 | Institute for Research in Biomedicine (IRB Barcelona)

nachricht Visualizing single molecules in whole cells with a new spin
13.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

A whole-body approach to understanding chemosensory cells

13.12.2017 | Health and Medicine

Water without windows: Capturing water vapor inside an electron microscope

13.12.2017 | Physics and Astronomy

Cellular Self-Digestion Process Triggers Autoimmune Disease

13.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>