Scripps Research Institute Scientists Report Breakthrough in DNA Editing Technology LA JOLLA, CA August 26, 2013 Scientists at The Scripps Research Institute (TSRI) have found a way to apply a powerful new DNA-editing technology more broadly than ever before.
This is one of the hottest tools in biology, and we've now found a way to target it to any DNA sequence, said Carlos F. Barbas III, the Janet and Keith Kellogg II Chair in Molecular Biology and Professor in the Department of Chemistry at TSRI.
The breakthrough concerns a set of designer DNA-binding proteins called TALEs, which biologists increasingly use to turn on, turn off, delete, insert or even rewrite specific genes within cells for scientific experiments and also for potential biotech and medical applications, including treatments for genetic diseases.
TALE-based methods had been considered useful against only a fraction of the possible DNA sequences found in animals and plants, but the new finding removes that limitation.
Barbas and his team report their finding on August 26, 2013 in an advance online edition of the journal Nucleic Acids Research.
Useful Tools
Molecular biologists have long dreamed of being able to manipulate DNA in living cells with ease and precision, and by now that dream is nearly a reality. TALE-based designer proteins, introduced just a few years ago, are arguably the most user-friendly and precise DNA-directed tools that have yet been invented.
Designer TALEs (transcription-activator-like effectors) are based on natural TALE proteins that are produced by some plant-infecting bacteria. These natural TALEs help bacteria subvert their plant hosts by binding to specific sites on plant DNA and boosting the activity of certain genes thereby enhancing the growth and survival of the invading bacteria.
Scientists have found that they can easily engineer the DNA-grabbing segment of TALE proteins to bind precisely to a DNA sequence of interest. Typically they join that DNA-binding segment to another protein segment that can perform some desired function at the site of interest for example, an enzyme fragment that cuts through DNA. Collectively the Barbas laboratory and others in this field have already engineered thousands of these powerful TALE-based DNA-editing proteins.
However, TALE-based DNA-editing has been seen to have a significant limitation. Virtually all the natural TALE proteins that have been discovered so far target sequences of DNA whose transcription begins with the nucleoside thymidine the letter T in the four-letter DNA code. Structural studies have hinted that natural TALE proteins can't bind well to DNA without that initial T. Molecular biologists thus have widely assumed that the same T restriction rule applies to any artificial TALE protein they might engineer.
Yet no one has investigated thoroughly whether that initial thymidine is truly required for the variety of TALE designer proteins and enzymes that now exist, said Brian M. Lamb, a research associate in the Barbas Laboratory who was first author of the new study.
Questioning Assumptions
Lamb started by evaluating how well TALE-based proteins function against their usual DNA targets when the first DNA letter is switched from a T to one of the other three nucleosides (A, G or C). Using a library of natural and engineered TALE proteins, he found strong evidence in favor of the T restriction rule. There was an orders-of-magnitude difference some of the TALE proteins we evaluated lost as much as 99.9% of their activity when we changed that first nucleoside base, said Lamb.
But he wasn't ready to give up on the possibility of designing more broadly useful TALE proteins. For this he adapted a directed evolution technique developed last year by Andrew C. Mercer, who at the time was a research associate in the Barbas laboratory. First, Lamb generated a large library of novel TALE proteins that vary randomly in the structures they hypothesized to grab the initial nucleoside. He then put these new TALEs through a series of tests, to select in a speeded up version of natural evolution those that work adequately even with a non-T nucleoside at the start of their target DNA sequence.
In this way, he found several new TALE protein architectures that aren't held back by the T restriction. One prefers to bind to DNA that begins not with a T nucleoside but with a G (guanosine). Others bind well enough to sequences that start with any of the four DNA nucleosides. Lamb found that these non-T-restricted TALEs work as designed when conjoined, for example, to DNA-cutting enzyme fragments. Essentially we abolished the T requirement, said Lamb.
That means that the number of DNA sites we can target with TALE-based proteins, and the precision with which we can target within any given gene, have gone up dramatically, Barbas said.
A Multitude of Potential Uses
He and his team plan to follow up the discovery mostly by using the new unrestricted TALE-based proteins as tools for developing potential gene therapies. But the removal of the T restriction on TALE-based DNA editing should have a positive impact also on basic molecular biology, biotechnology, stem cell medicine, and nanotechnology when they are combined for example with DNA origami. Indeed any application that requires the manipulation of DNA in living cells or even the construction of protein-DNA machines should benefit from this breakthrough.
The number of potential uses of this technology is probably more than any one person can imagine, Barbas said.
The study, Directed Evolution of the TALE N-Terminal Domain for Recognition of All 5' Bases, was funded in part by the National Institutes for Health Pioneer Award (grant DP1CA174426). For see the study, see http://nar.oxfordjournals.org/content/early/2013/08/26/nar.gkt754.full-text-lowres.pdf
Ab
Most recent headlines
17/02/2025
TVBEurope talks to the team who brought a piece of broadcasting history back to life on BBC Wales last night
By Jenny Priestley
Published: February 14, 2025 ...
17/02/2025
Eligible studios will receive the relief directly from their local authorities, with no need to submit a claim
By Matthew Corrigan
Published: February 17, 20...
17/02/2025
As DEI initiatives come under pressure in the USA, supporters of Rise, which promotes diversity in the media and entertainment sector, discuss the continuing im...
17/02/2025
EIB Global loan will partially fund SES's continued O3b mPOWER medium earth orbit (MEO) fleet expansion enabling additional capacity worldwide. O3b mPOWER s...
15/02/2025
At Nielsen, Business Resource Groups (BRGs) play a critical role in nurturing a ...
15/02/2025
Innovation to empower creativity: Explore the latest in Lightroom
Rob Christensen February 15, 2025
0 Comments
Whether you want to remove distracting ...
15/02/2025
Wisycom, a worldwide leader in RF technology and provider of wireless solutions, announces a new distribution agreement with EQUAPHON. An Argentinian profession...
15/02/2025
DPA Microphones, the leading manufacturer of high-quality microphone solutions, is pleased to welcome Nicholas Nick Mariano and Vincent Vince Divine to the ...
15/02/2025
Tuxera, a leading provider of quality-assured file systems and networking solutions, will showcase how Tuxera Fusion SMB enables unprecedented performance for m...
15/02/2025
Bitmovin's latest Video Developer Report indicates an increasing role of AI, the slow adoption of next-generation codecs, and continuing challenges when it ...
15/02/2025
When Michelin Enterprises set out to promote its prestigious Hotel Guide in the new Sleepless in the Kitchen , campaign, veteran German/Slovenian gaffer Robert...
15/02/2025
Formula E, the world's first all-electric racing series, revolutionizing motorsport with cutting-edge technology and a commitment to sustainability has sele...
15/02/2025
Agile Content, a global leader in TV and video technology solutions, announces its rebranding to AgileTV.
The transition to AgileTV stems from a commitment to ...
15/02/2025
Hiltron Communications will promote the latest additions to its range of satellite communication products, systems and supporting services at GovSatCom 2025. Th...
15/02/2025
Following the success of the original Airglow Booklight, DoPchoice debuts a new addition to their inflatable line the Float. This lightweight, inflatable, round...
15/02/2025
LAS VEGAS Marshall Electronics has announced that it will debut its newest camera controller, the RCP Plus, at the 2025 NAB Show at Booth N2649 between April 5 ...
15/02/2025
ATLANTA Gray Media has named Blake Sebo as the next general manager of KTUU and KYES, Gray's NBC and CBS affiliates in Anchorage, Alaska....
15/02/2025
KOKKEDAL, Denmark DPA Microphones will feature its new CORE+ technology for distortion-free microphone sound at the 2025 NAB Show, April 5-9, in Las Vegas....
15/02/2025
SWANSEA, U.K. QuickLink will launch StudioPro-NDI and StudioPro-3, two new models of its QuickLine StudioPro video production platform, at the 2025 NAB Show, Ap...
15/02/2025
Live From 2025 NBA All-Star Game Weekend: After 25 Years, Turner Sports All-In F...
15/02/2025
NASCAR Driver Cam on Max Embraces Cloud-Based Workflow for 2025 Season Chris Brown of WBD Sports says Mobii will play key part in delivering signals from the tr...
14/02/2025
Last month, we officially launched the Spotify Partner Program, a powerful new m...
14/02/2025
From an island off the coast of Lutruwita to the global stage in France SBS & ...
14/02/2025
The future of electro-optical/infrared (EO/IR) land systems is evolving so that ...
14/02/2025
Here are 5 reasons why you should attend ISE 2025
Discover more about Calrec: Learn more about Calrec's legacy of innovation in broadcast audio solutions ...
14/02/2025
World Radio Day: On the same wavelength
By Graham Murray, International Sales Manager at Calrec
To mark World Radio Day, Calrec's International Sales Ma...
14/02/2025
DALLAS and TYSONS, Va. Tegna has concluded a broadcast rights agreement that makes Tegna's KFAA in Dallas the exclusive local television partner of the Dall...
14/02/2025
Amazon's Prime Video has released a new app for Apple TV that the streamer said delivers an improved streaming experiences with faster scrolling, improved s...
14/02/2025
CLEVELAND Telos Alliance announced a software update for its Axia Quasar XR and SR line of audio-over-IP (AoIP) mixing consoles and will show the offering at th...
14/02/2025
Puget Systems Returns to HPA Tech Retreat 2025 with New Analysis Tools for Puge...
14/02/2025
Glass Animals: Tour of Earth Uses Blackmagic Live Production Workflow
Brie Clayton February 14, 2025
0 Comments
80six deploys Blackmagic URSA Broadcas...
14/02/2025
A dispute between Paramount and Youtube TV that would have pulled CBS stations and Paramount's cable channels from the streaming service has been temporaril...
14/02/2025
Colourist Deidre (Dee) McClelland details how she helped shape the distinct look and feel of whimsical Oscar-nominated stop-motion film, Memoir of a Snail
By C...
14/02/2025
BitFire said it intends to introduce forward-looking services that simplify the launch of live production workflows, and enhance real-time collaboration
By Jen...
14/02/2025
The claim by the liquidators is the latest twist in the ongoing saga of the companys collapse at the end of 2021
By Matthew Corrigan
Published: February 14, ...
14/02/2025
A carriage dispute between YouTube TV and Paramount could come to a head today (Feb. 13), with the virtual pay TV provider threatening to pull all of the progra...
14/02/2025
ENGLEWOOD CLIFFS, N.J. LG Electronics USA has opened a new in-house, state-of-the-art virtual production studio at its 360,000-square-foot North American headqu...
14/02/2025
NEW YORK In a bid to help local broadcasters find new ways of monetizing their content, the Coalition for Innovative Media Measurement (CIMM) and TVB have relea...
14/02/2025
WASHINGTON Three Democratic U.S. Senators have sent a stern letter blasting FCC Chair Brendan Carr for the weaponization of the agency for attacking broadcast...
14/02/2025
Years after launching the streaming service Apple TV+ in November of 2019, Apple has finally released a version of its steaming app for Android devices....
14/02/2025
FOOTHILL RANCH, Calif. Red Digital Cinema will make its V-RAPTOR [X] and KOMODO-X camera systems available with Nikon's premier Z Mount, providing filmmaker...
14/02/2025
DAYTONA, Fla. The Fox Sports production of this year's Daytona 500 will see the addition of a few new tech elements and the continued unfolding of the broad...
14/02/2025
Watch Bryson Battles Blind Audition on The Voice Get a Four-Chair Turn Michael Bubl said the Boston Conservatory at Berklee musical theater senior might have...
14/02/2025
2025 Daytona 500: FOX Sports Looks To Ride Super Bowl LIX Momentum Into NASCAR S...
14/02/2025
14 Feb 2025
VEON's Kyivstar and the Come Back Alive Foundation Raise USD 2....
14/02/2025
Max Renews THE PITT, Starring Noah Wyle, For A Second Season
Max
Warner Bros. Television Group
The Pitt
New Episodes Of The Medical Drama From John...
14/02/2025
This year, Technicolor proudly celebrates 110 years of shaping the magic of cinema pioneering color, visual effects, and innovation that bring unforgettable l...
14/02/2025
NBA All-Star: More Games, More Teams, More Music, More Sound From the Court Turner Sports' team will deploy familiar tech to capture all the audio By Dan D...
14/02/2025
LIV Golf Continues To Innovate With Drones, Data-Driven Graphics, and All-Access...
Scripps Research Institute Scientists Report Breakthrough in DNA Editing Technology LA JOLLA, CA August 26, 2013 Scientists at The Scripps Research Institute (TSRI) have found a way to apply a powerful new DNA-editing technology more broadly than ever before.
