Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

The structure-based design of zinc finger nucleases can facilitate genomic editing

20.05.2011
A recent study of significant research value carried out at the State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, China-Research, and published in the May 2011 issue of Science China Life Sciences (Issue 54) described a novel method using FoldX force field based protein modeling that can be applied in zinc finger nucleases design.

Zinc finger nucleases (ZFNs) can actively introduce a double-strand break (DSB) at target loci in eukaryotic genomes and this can improve the efficiency of gene knock-out or knock-in by several orders of magnitude. Therefore, ZFN is becoming a promising novel tool for genomic editing.

However, most current strategies for developing zinc finger nucleases with customized sequence specificities require the construction of numerous tandem arrays of zinc finger proteins (ZFPs), and the subsequent large-scale in vitro validation of their DNA binding affinities and specificities using bacterial selection. The labor and expertise required in this complex process limits the broad adoption of the ZFN technology.

In this work, an effective computational assisted design strategy was introduced to lower the complexity of the production of a pair of functional ZFNs. Dr. He and Prof. Chen used the FoldX force field to build 3D models of 420 ZFP-DNA complexes based on zinc finger arrays developed by the Zinc Finger Consortium using OPEN (oligomerized pool engineering). Using nonlinear and linear regression analysis, they found that the calculated protein-DNA binding energy in a modeled ZFP-DNA complex strongly correlates to the failure rate of the zinc finger array to show significant ZFN activity in human cells. In their models, less than 5% of the three-finger arrays with calculated protein-DNA binding energies lower than -13.132 kcal mol−1 failed to form active ZFNs in human cells. By contrast, for arrays with calculated protein-DNA binding energies higher than -5 kcal mol−1, as many as 40% of them lacked ZFN activity in human cells. Therefore, the FoldX force field based ZFN design strategy can be effectively used to reduce the failure rate and to increase efficiency in producing customized ZFNs.

"This is a novel strategy for designing customized ZFN pairs. It enables us to predict whether a candidate ZFN can function well in mammalian cells by calculating the protein-DNA binding energy within the modeled complex." was the opinion of one journal reviewer. "The authors tried a new method based on the FlodX force field to overcome the complex screening process in ZFN design. It appeared to be helpful to the rapid developed ZFN technology." commented another reviewer.

The authors are affiliated to The State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, China. The group mainly focuses on unraveling the genetic basis of economic traits and disease resistant capabilities in swine using comprehensive strategies that include the generation of transgenic or gene knock-out pig models.

Funding for the project was provided by the National Natural Science Foundation of China (Grant No. 30901018) and the China Postdoctoral Science Foundation (Grant No. 201003388).

Reference: He Z Y, Mei G, Zhao C P, et al. Potential application of FoldX force field based protein modeling in zinc finger nucleases design. Sci China Life Sci, 2011, 54: 1-8, doi: 10.1007/s11427-011-4159-9

ZuYong He | EurekAlert!
Further information:
http://zh.scichina.com/english/

More articles from Studies and Analyses:

nachricht WAKE-UP provides new treatment option for stroke patients | International study led by UKE
17.05.2018 | Universitätsklinikum Hamburg-Eppendorf

nachricht First form of therapy for childhood dementia CLN2 developed
25.04.2018 | Universitätsklinikum Hamburg-Eppendorf

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Powerful IT security for the car of the future – research alliance develops new approaches

The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.

Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

12th COMPAMED Spring Convention: Innovative manufacturing processes of modern implants

28.05.2018 | Event News

In focus: Climate adapted plants

25.05.2018 | Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

 
Latest News

International Workshop Sees Central Role for Solar in Transforming the World Energy Economy

28.05.2018 | Seminars Workshops

Cognitive Power Electronics 4.0 is gaining momentum

28.05.2018 | Trade Fair News

Organic light-emitting diodes become brighter and more durable

28.05.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>