Breaking News
December 17, 2017 - New Insight on Killer Fungus Threatening Bats
December 17, 2017 - Early Atherosclerosis Defies ‘Normal’ Cholesterol
December 17, 2017 - CRF1 stress receptor is regulator of mast cell activity during stress
December 17, 2017 - CREST Failed to Dampen Enthusiasm for Carotid Stenting in Elderly
December 17, 2017 - Rising levels of HIV drug resistance
December 17, 2017 - Aging brain’s failure to coordinate deep-sleep brainwaves makes older adults forget
December 17, 2017 - Rural Workers Have Higher Exposures to COPD-Causing Pollutants
December 17, 2017 - Don’t Delay Hip Fracture Surgery. Here’s Why: MedlinePlus Health News
December 17, 2017 - NIH launches HIV prevention trial of long-acting injectable medication in women
December 17, 2017 - Op-Ed: Get Ready for a Tsunami of ECGs
December 17, 2017 - Observation care may save more than thought
December 17, 2017 - Scientists explore effectiveness of action video games to combat dyslexia
December 17, 2017 - Teens Acting Badly? Smog Could Be to Blame
December 17, 2017 - FDA Says ‘Yes’ to Short-Acting Insulin Admelog
December 17, 2017 - Vaping popular among teens; opioid misuse at historic lows
December 17, 2017 - Lower Urinary Symptoms Occur in Almost All Patients with SSc
December 17, 2017 - Genetic mutation in extended Amish family in Indiana protects against aging and increases longevity (Update)
December 16, 2017 - Butler Hospital launches international Alzheimer’s disease prevention study
December 16, 2017 - iMedicalApps: Virtual Reality Boosts Self-Confidence for Med Students
December 16, 2017 - Researchers validate five new genes responsible for Amyotrophic Lateral Sclerosis
December 16, 2017 - New genetic analysis of candidiasis reveals surprising fungal sex secrets
December 16, 2017 - New high precision machine-learning model could help accelerate drug discovery
December 16, 2017 - Groundbreaking gene therapy trial brings cure for hemophilia closer
December 16, 2017 - Racial Differences Seen in IgG4 Disease
December 16, 2017 - Treacher Collins Syndrome
December 16, 2017 - New approach to tracking how deadly ‘superbugs’ travel could slow their spread
December 16, 2017 - Muscle paralysis may promote breakdown of bones
December 16, 2017 - WSU scientists create injectable dye to track progression of diseases
December 16, 2017 - Kaiser Permanente delivers clot-busting drugs to stroke patients more than twice as fast as national rates
December 16, 2017 - Some Great Holiday Foods for Weight Loss
December 16, 2017 - Shared Decision-Making Strategies for Lung Ca Screening Get High Marks
December 16, 2017 - Lactic acid bacteria can protect against Influenza A virus, study finds
December 16, 2017 - Cancer immunotherapy’s effectiveness may depend on patient’s genetic makeup
December 16, 2017 - Researchers explore patient-doctor conversations, best practices linked to opioid tapering
December 16, 2017 - ‘Virtual child’ to help professionals learn key techniques to treat children with autism
December 16, 2017 - IU scientists discover way to make drug treatment more successful against malaria
December 16, 2017 - Prostate cancer researchers find significant disparities between two liquid biopsy providers
December 16, 2017 - ED-Diagnosed Lung Ca Patients Worse Off: Clin Onc News Report
December 16, 2017 - Calcium in Urine Test: MedlinePlus Lab Test Information
December 16, 2017 - Pregnancy-related conditions taken together leave moms—and dads—at risk
December 16, 2017 - Research uncovers mechanism implicated in defective function of tumor-associated dendritic cells
December 16, 2017 - OncoBreak: Stubborn Racial Disparities; Paid Medical Leave & Chemo; DIY Gene Tests
December 16, 2017 - Critical link between obesity and diabetes has been identified
December 16, 2017 - Transfusion dependence reduces access to high-quality end-of-life care for leukemia patients
December 16, 2017 - Porvair and Suzhou Tianlong Bio to develop epigenetic analysis technologies
December 16, 2017 - FDA Approves Ixifi (infliximab-qbtx), a Biosimilar to Remicade
December 16, 2017 - Morning Break: Trump to Get Check-Up; Cancerous Transplant; Death Knell for MIPS?
December 16, 2017 - First transcatheter implant for diastolic heart failure successful
December 16, 2017 - ‘Sushi-like’ nanodiscs provide structural snapshots of misfolding proteins
December 16, 2017 - Inherited gene variation may be to blame for poor survival of patients with early-onset breast cancer
December 16, 2017 - Sign-up deadline is Friday, but some people may get extra time
December 16, 2017 - Higher Booze Taxes Might Pay Off for Public Health
December 16, 2017 - Regular Activity in Midlife Spares Joints in Women
December 16, 2017 - Rain May Not Cause Achy Joints After All: MedlinePlus Health News
December 16, 2017 - MedDiet adherence doesn’t affect acute heart failure mortality
December 16, 2017 - HKBU experts develop new generation of smart anti-cancer drug molecules
December 16, 2017 - Chronic Kidney Disease Audit finds wide variations in coding of CKD patients in primary care
December 16, 2017 - Scientists use nanoparticles to fight Mucoviscidosis
December 16, 2017 - Increasing physical activity decreases risk of death from lymphoma
December 16, 2017 - Fear compromises the health, well-being of immigrant families, survey finds
December 16, 2017 - Rejected antibiotic candidate could be worth a second look, research finds
December 16, 2017 - Is Nation on the Right Track to Combat Opioid Crisis?
December 16, 2017 - Arthritis No Longer Just a Disease of the Old: MedlinePlus Health News
December 16, 2017 - Study reveals biology behind why muscle stem cells respond differently to aging or injury
December 16, 2017 - Family members without inherited mutation have increased risk of melanoma
December 16, 2017 - Researchers reveal previously unknown mechanism that inhibits cells’ ability to develop into tumors
December 16, 2017 - Studies highlight potential of fMRI applications to detect, treat epilepsy in children
December 16, 2017 - Active surveillance proposed as first-line approach to manage patients with low-risk PMC of the thyroid
December 16, 2017 - Patients’ life values affect their attendance at medical treatment for pelvic-floor dysfunction
December 16, 2017 - Experts consider hazards of antibiotic resistances to be high
December 16, 2017 - Study finds erectile dysfunction as risk factor for early cardiovascular disease
December 16, 2017 - Amber-tinted glasses may reduce insomnia severity
December 16, 2017 - Arthritis Drug Seen Lowering GvHD Risk
December 16, 2017 - Atoh1, a potential Achilles’ heel of Sonic Hedgehog medulloblastoma
December 15, 2017 - Cornell engineers develop new method to measure vital signs using radio waves
December 15, 2017 - Rutgers studies highlight need for salon clients, workers to protect themselves from health risks
December 15, 2017 - FDA Approves Nucala (mepolizumab) for Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome)
December 15, 2017 - Morning Break: CVS Buying Aetna; Uterus Transplant Baby; Your Brain on Drugs, Redux
December 15, 2017 - Social phobia linked to autism and schizophrenia
December 15, 2017 - Timestrip technology helping to prevent missed vaccinations
TUM scientists build virus-sized structures using DNA origami technology

TUM scientists build virus-sized structures using DNA origami technology

image_pdfDownload PDFimage_print

It is the double strands of our genes that make them so strong. Using a technique known as DNA origami, biophysicist Hendrik Dietz has been building nanometer-scale objects for several years at the Technical University of Munich (TUM). Now Dietz and his team have not only broken out of the nanometer realm to build larger objects, but have also cut the production costs a thousand-fold. These innovations open a whole new frontier for the technology.

Viruses encapsulate their genetic material in a shell comprising a series of identical protein building blocks. The hepatitis B virus capsule, for example, comprises 180 identical subunits, a typical case of “prefabricated” construction deployed frequently in nature.

The team led by Hendrik Dietz, Professor of Biomolecular Nanotechnology at the TU Munich has now transferred viral construction principles to DNA origami technology. This allows them to design and build structures on the scale of viruses and cell organelles.

The technology builds on a long single strand that is appended to a double-stranded structure using short staple sequences. “The double-stranded structure is energetically sufficiently stable so that we can force the single strand into almost any shape using appropriately chosen counterparts,” explains Hendrik Dietz. “This way we can precisely design objects in the computer that are merely a few nanometers in size.”

Gears for nanomotors

The Dietz lab commands techniques that allow them to further modify and insert chemical functionalities into objects by adding side groups. But, until now, the size of the objects remained in the nanometer realm.In the renowned scientific journal Nature, the team now describes how larger structures can be built using prefabricated parts.

To this end, they first created V-shaped nano-objects. These have shape-complementary binding sites on their sides, allowing them to autonomously attach to each other while floating in a solution. Depending on the opening angle, they form “gears” with controlled number of spokes.

“We were thrilled to observe that, almost without exception, rings formed as defined by the opening angle,” says Hendrik Dietz. “Decisive for the ability to build objects of this size and complexity is the precision and rigidity of the individual building blocks. We had to reinforce individual elements with crossbars, for instance.”

Construction of microtubes

To further exploit the construction principle, the team created new building blocks that had “glue joints” not only on the sides, but also slightly weaker ones on the top and bottom. This allows the “nano-gears” to form long tubes using the additional docking sites in a second step.

“At lengths of one micrometer and a diameter of several hundred nanometers, these tubes have reached the size of some bacteria,” explains Hendrik Dietz. “And we can use the architecture of individual elements to determine features of the overall structure.”

Building polyhedral structures

Inspired by the symmetries and the hierarchical design of viruses, the researchers also attempted to build closed cage structures. “A potential future application of artificial cages is the transport of medication in the body,” explains Hendrik Dietz. “Here, the goal is to release active agents only at specific desired locations, sparing the rest of the body.”

Using the principles already applied to the structures described before, the team now constructed new elements they hoped would assemble in a self-limiting fashion into cage structures under the right conditions. According to these strategies, a triangular middle section and three V-shaped elements give rise to a three-pronged building element.

Depending on the opening angle of the V, a defined number of these units merge to form tetrahedral, hexahedral or dodecahedral structures in a second step. The final structures integrate up to 1.8 million addressable DNA base pairs at user-defined positions. For the first time, these discrete-size cages attain molecular weights and sizes comparable to that of viruses and small cell organelles.

Cost-effective mass production

To date, manufacturing processes have limited the scope of application to those requiring only small amounts of material. The fact that only a few micrograms can be manufactured with conventional methods precludes many potential medical and materials science applications.

The bottleneck is the short staple strands that must be chemically produced base by base. The main strand obtained from bacteriophages, on the other hand, can be produced on a large scale using biotechnological processes.

That is why the team led by Hendrik Dietz refined so-called DNA enzymes, a discovery stemming from synthetic biotechnology. These are DNA strands that break apart at specific positions when exposed to a high concentration of zinc ions.

They joined the short staple sequences to a long strand using two modified DNA enzymes each. “Once precisely assembled with a specific base sequence, these combined strands can be reproduced in a biotechnological process, as with single strands of bacteriophage DNA,” says Dietz, explaining the key feature of the process.

Biotechnological production on a large scale

Both the main strand and the secondary strand, comprising DNA enzymes and the staple sequences, were successfully produced using a high cell density process with bacteria. The process is scalable and thus amenable to high volume production of the main strands and staples. Increasing the zinc ion concentration after DNA isolation releases the short staple sequences, which then fold the main strand into the desired shape.

Extensive investigations of the reaction mechanisms in collaboration with colleagues at the Institute of Biochemical Engineering showed that this is possible even on a large scale. At the TUM Research Center for Industrial Biotechnology in Garching, scientists have now produced multiple grams of four different DNA origami objects. Scaling up the process to a cubic meter scale is now within grasp.

“The interplay of biotechnology and process technology has thus enabled setting a truly fundamental milestone on the path to future applications in DNA nanotechnology,” says Professor Dirk Weuster-Botz, Chair of the Institute of Biochemical Engineering.

Source:

https://www.tum.de/nc/en/about-tum/news/press-releases/detail/article/34360/

Tagged with:

About author

Related Articles