Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


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

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:

More articles from Studies and Analyses:

nachricht Diagnoses: When Are Several Opinions Better Than One?
19.07.2016 | Max-Planck-Institut für Bildungsforschung

nachricht High in calories and low in nutrients when adolescents share pictures of food online
07.04.2016 | University of Gothenburg

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: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>