Background of Genome Editing for Lysosomal Storage Diseases
Lysosomal storage diseases (LSDs) are a collection of more than 50 severe genetic disorders caused by deleterious mutations. They are monogenic, and most of them present with a large number of mutations. The advent of DNA recombination technology, which can deliver "new genes" to patient cells, offers hope for a cure for LSDs. Scientists have developed CRISPR/Cas9 (clustered regularly spaced short palindromic repeats/caspase 9), a relatively new technology based on the use of guided RNA to direct "molecular scissors" to specific sites in the genome and cut double-stranded DNA by the nucleic acid endonuclease Cas9. Thereafter, the double-stranded DNA is repaired by adding donor DNA. The double-stranded DNA break is repaired by the addition of donor DNA, leading to controlled gene modifications. This technique is currently being applied in vitro to human induced pluripotent stem cells (iPSCs) as a form of gene therapy to correct a variety of serious genetic disorders. With years of experience in developing gene therapy strategies for LSDs, CD BioSciences is committed to providing customers worldwide with CRISPR/Cas9 based genome editing solutions for LSDs, enabling the selective correction of deleterious mutations in a patient's own genome to the correct nucleotide base sequences.
Genome Editing Solutions for Lysosomal Storage Diseases
Our ex vivo gene therapy and in vivo gene therapy strategies for LSDs rely on gene enhancement rather than correction of deleterious mutations in the patient's genome. Working closely with genome engineering biologists, we attempt to use nucleases for genome editing to provide a simpler and safer solution for targeted gene modification in LSDs. Our genome editing strategy aims to manipulate the patient's genome in a controlled manner.
We have successfully built an elegant and easy-to-use CRISPR/Cas9 gene editing system platform that allows selective targeting in vitro and in vivo of genes containing mutations causing non-functional products and correcting disease-causing mutations. Our team of experts is dedicated to maximizing the potential of CRISPR/Cas9 applications in the field of LSDs, including:
- Creating new models of LSD disease.
- Developing potential therapeutic strategies, such as inserting therapeutic cDNA sequences into different loci within the genome.
The major drawbacks of hematopoietic stem cell transplantation (HSCT) include the significant risks associated with the procedure, such as the potential for graft-versus-host disease, difficulty in finding HLA-compatible donors and chimeras. Our expert team develop a combination of CRISPR/Cas9 technology with HSCT to provide customized treatment options for LSDs.
(1) We transfect hematopoietic stem cells derived from mice with vectors encoding custom endonucleases and donor vectors to guide homologous recombination.
(2) Corrected cells were selected by ex vivo and implanted back into the mice.
Advantages of the Genome Editing Solutions
- Endonucleases are customized molecular scissors that allow DNA to be cut into well-defined, perfectly specified fragments in virtually all cell types.
- Endonucleases can be delivered to cells by transiently expressing nuclease plasmids or by transcribed RNA, thus avoiding the use of viruses.
- Genome editing in combination with HSCT avoids rejection reactions.
- There is a wealth of animal and in vitro studies to validate the reliability of CRISPR/Cas9 technology.
- CRISPR/Cas9 is easy to design, relatively low cost, and has the ability to alter a large number of genes.
We are very innovative in the development phase to achieve each client's individual goals. We are ready to explore the value of genome editing technology to meet the requirements of novel LSDs treatment strategies. For more information, please feel free to contact us.
Reference
- de Carvalho T G, da Silveira Matte U, Giugliani R, et al. (2015) Genome editing: potential treatment for lysosomal storage diseases[J]. Current Stem Cell Reports. 1(1): 9-15.