Meganuclease Based Gene Engineering Service
Gene editing therapies are emerging as a promising approach to help patients suffering from rare genetic diseases. Through our meganuclease-based gene editing platform, our company helps customers develop product candidates aimed at addressing previously intractable indications using novel therapeutic modalities such as gene editing.
Meganuclease is an endodeoxyribonuclease with a large recognition site profile. The ability of this highly specific enzyme to target individual DNA breaks in complex genomes and achieve gene modifications while avoiding random off-targeting makes it an ideal starting material for therapeutic-grade genome editing technologies. Since most genetic diseases are caused by the absence of important proteins, this technology platform is well-suited for rare disease drug development.
Meganuclease is highly advantageous for use in the development of disease therapies due to its high specificity. These enzymes can be used as scaffolds to develop custom gene-targeting tools for cell line development or gene therapy. For example, a gene-editing strategy based on meganuclease has been developed for the treatment of Duchene muscular dystrophy, which restores the open reading frame of mutated muscular dystrophy genes. Furthermore, the homing nuclease I-CreI from the Chlamydomonas reinhardtii chloroplast genome was used to treat diseases caused by heterogeneous mitochondrial DNA mutations, and it can be applied for mtDNA editing to achieve specific elimination of mtDNA.
Fig. 1 Re-engineering meganuclease specificity: an example of a custom meganuclease targeting the sequence from the human XPC gene. (Silva G, et al., 2011)
Our Targeted Approaches
In the area of gene therapy for rare diseases, we help customers with targeted gene insertion or targeted correction to replace classical gene transfer leading to random integration into the genome, with our targeting strategies including:
- Targeted strategies based on recombinases
- Targeted strategies based on transposons
- Targeted strategies based on homologous recombination
- Targeted strategies based on non-homologous end-joining
We provide our customers with pre-designed meganucleases for genome editing. To meet the broad scientific needs of our customers, we also offer meganuclease modification services as well as the re-engineering of a large number of I-CreI derivatives into custom enzymes for specific target DNA sequences of interest. Our gene editing services include, but are not limited to:
- Meganuclease design
The development of artificial endonucleases with tailored specificity is critical for gene therapy to introduce transgenes or correct mutated genes at selected loci. However, off-site cleavage can lead to toxic effects on cells. We provide our customers with custom-designed meganucleases to effectively address this issue. Currently, we have designed several meganucleases that target genes involved in severe combined immunodeficiency (SCID) and other genetic diseases that can be treated with cellular therapies. We also help our customers design mitochondria-targeted meganucleases to develop gene therapies for rare mitochondrial diseases. These modified endonucleases have the potential to be ideal tools for genomic surgery.
- Improvement of meganuclease specificity
We help our customers design I-CreI dimerization interfaces to produce the second generation of functionally tailored meganucleases that meet high standards of specificity and non-toxicity. We provide our customers with data to monitor the specificity of meganucleases to ensure their efficacy in therapeutic applications.
- Meganuclease delivery
We help customers design lentiviral vectors for the transduction of engineered meganucleases, such as a method based on Vpr fusions.
- Development of gene therapy based on meganuclease
We offer our customers a variety of strategies for meganuclease-based gene therapy, including:
- Gene correction approaches
- Insertion of therapeutic genes into a safe harbor
- Targeted mutagenesis of human genes
- Virus clipping
Our company is committed to providing meganuclease-based gene-editing services to accelerate the development of safer and more effective gene therapies for rare diseases. If you need technical support and services in the field of gene editing, please contact us for more details.
- Silva, G.; et al. Meganucleases and other tools for targeted genome engineering: perspectives and challenges for gene therapy. Current gene therapy, 2011, 11(1): 11-27.
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