Meganucleases

As a pioneer in the field of genome engineering and in particular with the use of Meganucleases, Cellectis Cellectis group has extensive experience and has largely demonstrated its expertise through numerous scientific publications.

5′-Cytosine-Phosphoguanine (CpG) Methylation Impacts the Activity of Natural and Engineered Meganucleases
Valton, J., et al., The Journal of Biochemical Chemistry, 30139-30150. , Jun 2012
In this study, we asked whether CpG methylation could influence the DNA binding affinity and activity of meganucleases used for genome engineering applications. A combination of biochemical and structural approaches enabled us to demonstrate that CpG methylation decreases I-CreI DNA binding affinity and inhibits its endonuclease activity in vitro.
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Non-specific protein-DNA interactions control I-CreI target binding and cleavage
Molina, R., et al., Nucleic Acids Research, [Epub ahead of print], 2012
Homing endonucleases represent protein scaffolds that provide powerful tools for genome manipulation, as these enzymes possess a very low frequency of DNA cleavage in eukaryotic genomes due to their high specificity.
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Chromosomal context and epigenetic mechanisms control the efficacy of genome editing by rare-cutting designer endonucleases
Daboussi, F., et al., Nucleic Acids Research, [Epub ahead of print], 2012
The ability to specifically engineer the genome of living cells at precise locations using rare-cutting designer endonucleases has broad implications for biotechnology and medicine, particularly for functional genomics, transgenics and gene therapy.
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Identification of genes regulating gene targeting by a high-throughput screening approach
Delacôte, F., et al., Journal of Nucleic Acids, Epub 2011 Feb 13, 2011
Homologous gene targeting (HGT) is a precise but inefficient process for genome engineering. Several methods for increasing its efficiency have been developed, including the use of rare cutting endonucleases. However, there is still room for improvement, as even nuclease-induced HGT may vary in efficiency as a function of the nuclease, target site, and cell type considered.
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Context dependence between subdomains in the DNA binding interface of the I-CreI homing endonuclease
Grizot, S., et al., Nucleic Acids Research, 39, 6124-36, 2011
Homing endonucleases (HE) have emerged as precise tools for achieving gene targeting events. Redesigned HEs with tailored specificities can be used to cleave new sequences, thereby considerably expanding the number of targetable genes and loci.
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Meganuclease-mediated inhibition of HSV1 infection in cultured cells
Grosse, S., et al., Molecular Therapy, 19, 694-702, 2011
Herpes simplex virus type 1 (HSV1) is a major health problem. As for most viral diseases, current antiviral treatments are based on the inhibition of viral replication once it has already started. As a consequence, they impair neither the viral cycle at its early stages nor the latent form of the virus, and thus cannot be considered as real preventive treatments.
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