CRISPR/Cas9-based Therapy Development Platform
CRISPR/Cas9 is a commonly used gene-editing tool that can add, remove, or alter genetic material at particular locations in the genome. With a professional technical team and a complete genome editing platform, our company's CRISPR/Cas9-based therapy development service can provide a full set of gene therapy solutions. We customize personalized solutions according to your scientific research needs and provide cost-effective and professional services to accelerate your gene therapy research and development for rare diseases.
Introduction to CRISPR/Cas9
CRISPR/Cas9, also known as clustered regularly interspaced short palindromic repeats or CRISPR-associated nuclease 9, is an RNA-guided targeted genome editing technology adapted from the antiviral immune response of bacteria. The CRISPR/Cas9 system consists of two elements, sgRNA (single-guide RNA) and Cas9 protein.
Fig.1 Applications of CRISPR-Cas9 based gene engineering. (Wang, Yu, et al., 2019)
Usually, sgRNA guides the Cas9 protein to recognize the genome. With the protospacer-adjacent motif (PAM - the sequence NGG) present at the 3' end. Cas9 can cleave specific sites in the genome to form double strand breaks (DSBS). Double-strand breaks are usually repaired through non-homologous end joining, which usually deletes or changes the nucleotide at the site where the joining occurs. If Cas9 has one nuclease site inactivated, it will produce a single-stranded break in the target sequence. In the presence of recombinant donor DNA fragments, homologous DNA recombination sometimes changes the sequence of the break site to match the sequence of the donor DNA.
CRISPR/Cas9-based Therapy for Rare Diseases
CRISPR/Cas9-based therapy can be used to change the DNA of cells or organismsCas9-based be used for therapeutics research of rare diseases, such as cystic fibrosis, hemophilia, β-thalassemia, Huntington's, Parkinson's, tyrosinemia, Alzheimer's, Duchenne muscular dystrophy, Tay-Sachs, and fragile X syndrome disorders. Currently, there are already some cases of using CRISPR/Cas9-based therapy to treat rare diseases:
Table 1 Rare disease product pipelines of leading companies based on
CRISPR/Cas9-based therapy. (Mani, Indra., 2021)
| Rare Disease | Companies | Mechanism | Delivery | Notes |
|---|---|---|---|---|
| a-1-Antitrypsin deficiency | EDIT | NHEJ & HDR | In vivo | By AAV or LNP |
| NTLA | n/a | In vivo | By LNP | |
| Amyotrophic lateral sclerosis | CRSP | n/a | In vivo | Collaboration with Target ALS and University of Florida |
| Autoimmune and inflammatory diseases | NTLA | n/a | Ex vivo | Disease unspecified |
| β-Hemoglobinopathies (β-thalassemia & sickle cell disease) | CRSP | NHEJ | Ex vivo | CTX001;based on induction of y-globin |
| EDIT | NHEJ & HDR | Ex vivo | By RNP | |
| NTLA | n/a | Ex vivo | In collaboration with Novartis Institute for Biomedical Research, Inc. | |
| Cystic fibrosis | CRSP | HDR | In vivo | Correction/insertion of CFTR gene |
| EDIT | NHE & HDR | In vivo | By AAV or LNP | |
| Duchenne muscular dystrophy | CRSP | NHEJ | In vivo | Functional correction of DMD gene by deletion |
| EDIT | NHEJ | In vivo | Correction by small and large deletion; by AAV or LNP | |
| Friedreich's ataxia | CRSP | n/a | In vivo | Collaboration with Friedreich's Ataxia Alliance & University of Alabama (Birmingham) |
| Glycogen storage disease Ia | CRSP | HDR | In vivo | Correction/insertion of G6PC gene |
| Hemophilia | CRSP | HDR | In vivo | Withdrawn from portfolio Q3/4 2018 |
| Hurler Syndrome | CRSP | HDR | Ex vivo | Correction/insertion of IDUA gene |
| Inborn errors of metabolism | NTLA | n/a | In vivo | Disease unspecified; by LNP |
| Leber congenital amaurosis 10 | EDIT | NHEJ | In vivo | Correction by small deletion; by local AAV injection |
| Liver diseases | NTLA | n/a | Ex vivo | Disease unspecified |
| Primary hyperoxaluria type 1 | NTLA | na | In vivo | By LNP |
| Severe combined immunodeficiency | CRSP | HDR | Ex vivo | Withdrawn from portfolio Q3/4 2018 |
| Transthyretin amyloidosis | NTLA | n/a | In vivo | By LNP: collaboration with Regeneron Pharmaceuticals, Inc. |
| Usher syndrome 2a | EDIT | NHEJ | In vivo | By local AAV injection |
Our Services
With extensive experience in gene therapy development, our company provides you with a CRISPR/Cas9-based therapy development service to edit and treat any DNA mutations associated with rare diseases and provides you with one-stop solutions to accelerate your research and development of rare disease therapies.
CRISPR/Cas9 System Development
According to different disease types and therapeutics requirements, our company designs and develops suitable CRISPR/Cas9 systems, including selecting the appropriate Cas protein, designing and synthesizing gRNA, and providing you with precise gene editing for your rare disease gene therapy research.
CRISPR/Cas9 System Delivery
Based on specific application needs and cell types, our company uses viral vector and non-viral vector delivery strategies to provide you with efficient, low-toxicity, and highly specific CRISPR/Cas9 system delivery services. Support your rare disease gene therapy research by building the cell models needed for gene therapy, or by repairing genetic mutations in vivo through gene editing.
Off-target Effect Analysis
Our company provides comprehensive and accurate CRISPR/Cas9 off-target effect detection and analysis services to improve the safety of CRISPR/Cas9-based therapies. The analysis methods we use include but are not limited to:
- Whole Genome Sequencing
- LAM-HTGTS
- Digenome-Seq
- BLESS
Project Workflow
With a research team with extensive expertise, our company is confident to provide clients with CRISPR/Cas9-based therapy development services. We have the capabilities and resources to provide professional communication and problem-solving support to ensure that we can quickly respond to the changing needs of your rare disease therapy research projects. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Wang, Yu, et al. "A highly efficient CRISPR-Cas9-based genome engineering platform in Acinetobacter baumannii to understand the H2O2-sensing mechanism of OxyR." Cell Chemical Biology 26.12 (2019): 1732-1742.
- Mani, Indra. "CRISPR-Cas9 for treating hereditary diseases." Progress in Molecular Biology and Translational Science 181 (2021): 165-183.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.