Sigma-Aldrich Launches High-Fidelity CRISPRs to Enable Precise Gene Editing for Academic and Industrial Applications

Innovative paired-nickase design provides breakthrough that minimizes off-target effects to accelerate genetic research

May 06, 2014, 07:00 ET from Sigma-Aldrich Corporation

ST. LOUIS, May 6, 2014 /PRNewswire/ -- Sigma-Aldrich Corporation (Nasdaq: SIAL) today announced the availability of high-fidelity Sigma® CRISPR paired nickases, a novel patent-pending gene editing tool that can be easily and inexpensively employed in academic, agricultural, pharmaceutical, human health and other applications. The high-fidelity CRISPR technology has been designed to reduce unintended off-target gene modifications, providing the research community with a robust, reliable and precise tool to  interrogate and modify plant, animal, and human biology.

Sigma-Aldrich has engineered and developed high-fidelity CRISPRs to reduce unwanted DNA modifications by employing a paired nickase approach.  Single unmodified CRISPRs can cause specific double stranded breaks in DNA but they are also prone to cause off-target gene modifications1-5.  In contrast, a pair of Sigma-Aldrich high-fidelity CRISPR nickases may be used to make nicks in close proximity and on opposite DNA strands in order to generate a double stranded break. This design dramatically reduces the likelihood of generating off-target gene changes, while maintaining the ability to yield highly efficient and specific gene modifications.  

"Sigma-Aldrich is a leader in developing and supplying genetic manipulation technologies.  Our siRNA and shRNAs are widely used for gene knockdown studies and our CompoZr® Zinc Finger Nucleases for precise genomic editing.  Now, our high-fidelity CRISPRs are making precise genetic manipulation available for a wider range of applications," said Shaf Yousaf, Vice President, Technology and Business Development at Sigma-Aldrich.

"Just as Sigma-Aldrich improved and reduced the cost of zinc finger nucleases with CompoZr® zinc finger technology nucleases to provide the research community access to this gold-standard method for genome editing, our laboratories have worked to advance CRISPR engineering to attenuate its chief disadvantage - off-target activity - to offer scientists the fastest, most economical source for quality CRISPR designs," said Greg Davis, Ph.D., Principal Investigator, R&D at Sigma-Aldrich.

Genome editing with CRISPR RNA-guided nucleases has quickly gained popularity due to the relatively simplistic design process and their ability to efficiently modify or add genes in multiple species.  To accelerate gene editing research, Sigma-Aldrich's exclusive online bioinformatics tool is available to quickly generate high-fidelity CRISPRs against desired targets in human, rat, and mouse exomes. For other organisms or for more sophisticated applications, Sigma-Aldrich's expert genome editing bioinformatics team, which has developed advanced design toolsets based on cutting-edge public and proprietary CRISPR guidelines, can be consulted at no charge. Visit for additional information and to access these tools.

Sigma-Aldrich conveniently supplies its CRISPRs in plasmid and RNA-only formats to meet a wide variety of delivery needs for cell culture and embryo microinjection in health and industrial applications.

When investigators require greater specificity than existing CRISPR applications can provide, Sigma-Aldrich's CompoZr zinc finger nucleases provide a high-fidelity option with a well-published track record of preserving genomic integrity and well-defined intellectual property.



Cong, L. et al. Multiplex genome engineering using CRISPR/Cas systems. Science 339, 819—823 (2013).


Fu, Y. et al. High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells. Nat. Biotechnol. 31, 822–826 (2013).


Hsu, P. D. et al. DNA targeting specificity of RNA-guided Cas9 nucleases. Nat. Biotechnol. 31, 827–832 (2013).


Jiang, W., Bikard, D., Cox, D., Zhang, F. & Marraffini, L. A. RNA-guided editing of bacterial genomes using CRISPR-Cas systems. Nat. Biotechnol. 31, 233–239 (2013).


Pattanayak, V. et al. High-throughput profiling of off-target DNA cleavage reveals RNA-programmed Cas9 nuclease specificity. Nat. Biotechnol. 31, 839–843 (2013).

About Sigma-Aldrich: Sigma-Aldrich, a leading Life Science and High Technology company focused on enhancing human health and safety, manufactures and distributes 230,000 chemicals, biochemicals and other essential products to more than 1.4 million customers globally in research and applied labs as well as in industrial and commercial markets. With three distinct business units – Research, Applied and SAFC Commercial – Sigma-Aldrich is committed to enabling science to improve the quality of life. The Company operates in 37 countries, has more than 9,000 employees worldwide and had sales of $2.7 billion in 2013. For more information about Sigma-Aldrich, please visit its website at

Sigma-Aldrich, Sigma, and CompoZr are trademarks of Sigma-Aldrich Co, LLC registered in the US and other countries.  

SOURCE Sigma-Aldrich Corporation