Tag Archives: AuraSense

Sticky-flares nanotechnology to track and observe RNA (ribonucleic acid) regulation

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I like the name ‘sticky-flares’ and had hoped there was an amusing story about its origins. Ah well, perhaps I’ll have better luck next time.

This work comes out of Chad Mirkin’s lab at Northwestern University (Chicago, US) according to a July 21, 2015 news item on Azonano,

RNA [ribonucleic acid] is a fundamental ingredient in all known forms of life — so when RNA goes awry, a lot can go wrong. RNA misregulation plays a critical role in the development of many disorders, such as mental disability, autism and cancer.

A new technology — called “Sticky-flares” — developed by nanomedicine experts at Northwestern University offers the first real-time method to track and observe the dynamics of RNA distribution as it is transported inside living cells.

A July 20, 2015 Northwestern University news release by Erin Spain, which originated the news item, describes the research in a little more detail also including information about predecessor technology,

Sticky-flares have the potential to help scientists understand the complexities of RNA better than any analytical technique to date and observe and study the biological and medical significance of RNA misregulation.

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Previous technologies made it possible to attain static snapshots of RNA location, but that isn’t enough to understand the complexities of RNA transport and localization within a cell. Instead of analyzing snapshots of RNA to try to understand functioning, Sticky-flares help create an experience that is more like watching live-streaming video.

“This is very exciting because much of the RNA in cells has very specific quantities and localization, and both are critical to the cell’s function, but until this development it has been very difficult, and often impossible, to probe both attributes of RNA in a live cell,” said Chad A. Mirkin, a nanomedicine expert and corresponding author of the study. “We hope that many more researchers will be able to use this platform to increase our understanding of RNA function inside cells.”

…

Sticky-flares are tiny spherical nucleic acid gold nanoparticle conjugates that can enter living cells and target and transfer a fluorescent reporter or “tracking device” to RNA transcripts. This fluorescent labeling can be tracked via fluorescence microscopy as it is transported throughout the cell, including the nucleus.

In the … paper, the scientists explain how they used Sticky-flares to quantify β–actin mRNA in HeLa cells (the oldest and most commonly used human cell line) as well as to follow the real-time transport of β–actin mRNA in mouse embryonic fibroblasts.

Sticky-flares are built upon another technology from Mirkin’s group called NanoFlares, which was the first genetic-based approach that is able to detect live circulating tumor cells out of the complex matrix that is human blood.

NanoFlares have been very useful for researchers that operate in the arena of quantifying gene expression. AuraSense, Inc., a biotechnology company that licensed the NanoFlare technology from Northwestern University, and EMD-Millipore, another biotech company, have commercialized NanoFlares. There are now more than 1,700 commercial forms of NanoFlares sold under the SmartFlareä name in more than 230 countries.

The Sticky-flare is designed to address limitations of SmartFlares, most notably their inability to track RNA location and enter the nucleus. The Northwestern team believes Sticky-flares are poised to become a valuable tool for researchers who desire to understand the function of RNA in live cells.

Based on the paragraph about the precursor technology’s commercial success , I gather they are excited about similar possibilities for sticky-flares.

Here’s a link to and a citation for the paper,

Quantification and real-time tracking of RNA in live cells using Sticky-flares by William E. Briley, Madison H. Bondy, Pratik S. Randeria, Torin J. Dupper, and Chad A. Mirkin. Published online before print July 20, 2015, doi: 10.1073/pnas.1510581112 PNAS July 20, 2015

This paper is behind a paywall.

Chad Mirkin, spherical nucleic acids, and a new ‘periodic table’

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There was a big splash in July 2012 with the announcement that Chad Mirkin’s team at Northwestern University (Chicago, Illinois) had devised a skin cream that penetrated the skin barrier to deliver medication (my July 4, 2012 posting),

A team led by a physician-scientist and a chemist — from the fields of dermatology and nanotechnology — is the first to demonstrate the use of commercial moisturizers to deliver gene regulation technology that has great potential for life-saving therapies for skin cancers.

The topical delivery of gene regulation technology to cells deep in the skin is extremely difficult because of the formidable defenses skin provides for the body. The Northwestern approach takes advantage of drugs consisting of novel spherical arrangements of nucleic acids. These structures, each about 1,000 times smaller than the diameter of a human hair, have the unique ability to recruit and bind to natural proteins that allow them to traverse the skin and enter cells.

Mirkin has just finished presenting (Feb. 15, 2013 and Feb. 17, 2013) more information about spherical nucleic acids and their implications at the AAAS  (American Association for the Advancement of Science) 2013 meeting in Boston, Massachusetts. From the Feb. 15, 2013 news release on EurekAlert,

Northwestern University’s Chad A. Mirkin, a world-renowned leader in nanotechnology research and its application, has invented and developed a powerful material that could revolutionize biomedicine: spherical nucleic acids (SNAs).

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Potential applications include using SNAs to carry nucleic acid-based therapeutics to the brain for the treatment of glioblastoma, the most aggressive form of brain cancer, as well as other neurological disorders such as Alzheimer’s and Parkinson’s diseases. Mirkin is aggressively pursuing treatments for such diseases with Alexander H. Stegh, an assistant professor of neurology at Northwestern’s Feinberg School of Medicine.

“These structures are really quite spectacular and incredibly functional,” Mirkin said. “People don’t typically think about DNA in spherical form, but this novel arrangement of nucleic acids imparts interesting chemical and physical properties that are very different from conventional nucleic acids.”

Spherical nucleic acids consist of densely packed, highly oriented nucleic acids arranged on the surface of a nanoparticle, typically gold or silver.  [emphasis mine] The tiny non-toxic balls, each roughly 15 nanometers in diameter, can do things the familiar but more cumbersome double helix can’t do:

  • SNAs can naturally enter cells and effect gene knockdown, making SNAs a superior tool for treating genetic diseases using gene regulation technology.
  • SNAs can easily cross formidable barriers in the human body, including the blood-brain barrier and the layers that make up skin.
  • SNAs don’t elicit an immune response, and they resist degradation, resulting in longer lifetimes in the body.

“The field of medicine needs new constructs and strategies for treating disease,” Mirkin said. “Many of the ways we treat disease are based on old methods and materials. Nanotechnology offers the ability to rapidly create new structures with properties that are very different from conventional forms of matter.”

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“We now can go after a whole new set of diseases,” Mirkin said. “Thanks to the Human Genome Project and all of the genomics research over the last two decades, we have an enormous number of known targets. And we can use the same tool for each, the spherical nucleic acid. We simply change the sequence to match the target gene. That’s the power of gene regulation technology.”

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A member of President Obama’s Council of Advisors on Science and Technology, Mirkin is known for invention and development of biological and chemical diagnostic systems based upon nanomaterials. He is the inventor and chief developer of Dip-Pen Nanolithography, a groundbreaking nanoscale fabrication and analytical tool, and is the founder of four Chicago-based companies: AuraSense, AuraSense Therapeutics, Nanosphere and NanoInk.

Mirkin, in addition to his work with spherical nucleic acids, has been busy with other nanoparticles and possible dreams of a new ‘periodic table of elements’, from the Feb. 17, 2013 news release on EurekAlert,

Forging a new periodic table using nanostructures

Northwestern University’s Chad A. Mirkin, …, has developed a completely new set of building blocks that is based on nanoparticles and DNA. Using these tools, scientists will be able to build — from the bottom up, just as nature does — new and useful structures.

…

“We have a new set of building blocks,” Mirkin said. “Instead of taking what nature gives you, we can control every property of the new material we make. We’ve always had this vision of building matter and controlling architecture from the bottom up, and now we’ve shown it can be done.”

Using nanoparticles and DNA, Mirkin has built more than 200 different crystal structures with 17 different particle arrangements. Some of the lattice types can be found in nature, but he also has built new structures that have no naturally occurring mineral counterpart.

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Mirkin can make new materials and arrangements of particles by controlling the size, shape, type and location of nanoparticles within a given particle lattice. He has developed a set of design rules that allow him to control almost every property of a material.

New materials developed using his method could help improve the efficiency of optics, electronics and energy storage technologies. “These same nanoparticle building blocks have already found wide-spread commercial utility in biology and medicine as diagnostic probes for markers of disease,” Mirkin added.

With this present advance, Mirkin uses nanoparticles as “atoms” and DNA as “bonds.” He starts with a nanoparticle, which could be gold, silver, platinum or a quantum dot, for example. The core material is selected depending on what physical properties the final structure should have.

He then attaches hundreds of strands of DNA (oligonucleotides) to the particle. The oligonucleotide’s DNA sequence and length determine how bonds form between nanoparticles and guide the formation of specific crystal lattices.

“This constitutes a completely new class of building blocks in materials science that gives you a type of programmability that is extraordinarily versatile and powerful,” Mirkin said. “It provides nanotechnologists for the first time the ability to tailor properties of materials in a highly programmable way from the bottom up.”

If I read these two news releases rightly, the process (nanoparticles as atoms and DNA as bonds), Mirkin uses to create new structures is the same process he has used to create spherical nucleic acids. Given Mirkin’s entrepreneurial inclinations, I am curious as to how many and what kind of patents might be ‘protecting’ this work.