Background of Ex Vivo Gene Therapy for LSDs
Gene therapy has been proposed as a promising strategy to treat lysosomal diseases and improve the prognosis of affected patients. The goal is to provide patients with lysosomal storage disorders (LSDs) with therapeutic levels of the defective enzyme, which can be achieved by either ex vivo or direct in vivo gene therapy strategies. Among these, ex vivo gene therapy for LSDs is to harvest different cell types at different stages of maturation from patients, genetically modify the cells in vitro using gene therapy vectors, and reintroduce them as therapeutic agents into patients with LSDs to provide the defective cells in the affected tissues with the enzyme. Notably, the corrected cells can replace their enzymatically defective equivalents to produce resident and metabolically competent cell populations. With years of experience in developing gene therapy strategies for LSDs, CD BioSciences is committed to providing clients worldwide with ex vivo gene therapy strategies for LSDs based on ex vivo modification and transplantation of the modified cells into patients.
Solutions
The primary goal of our ex vivo gene therapy strategies for LSDs is to genetically modify cells in vitro. We develop the following two approaches to meet the needs of our clients.
Genetically Modified Stem Cells
Selecting the right cells is critical to help your project succeed. We offer an abundant supply of stem cells for ex vivo gene therapy in animal models of LSDs, including hematopoietic stem cells and neural stem cells.
In addition, we develop a variety of viral vectors (e.g., lentiviruses and γ retroviruses) as well as liposomes or other types of nanoparticles to genetically modify both of these cells, allowing for the expression of higher than normal levels of therapeutic enzymes and being a quantitatively more efficient source of enzymes than normal donor cells at the level of affected tissues in mice with LSDs. Our expert team helps you to efficiently transfer the gene into the autologous cells to be transplanted and is strictly dependent on the use of appropriate vectors. We offer a customized process for hematopoietic stem cell gene therapy for LSDs.
(1) Collection of autologous hematopoietic stem cells from the animal.
(2) The collected HSCs are genetically modified by transducing a viral vector with a therapeutic gene.
(3) Transplantation of the transduced HSCs into an animal model of LSDs for regulatory therapy.
Genetically Modified Artificial Organoid
We have successfully established an artificial organoid platform. Our expert team of organoids is genetically modified to overexpress lysosomal enzymes as a reservoir for defective enzymes. The advantages of this approach include the ability to stably modify cells using viral or non-viral methods, the ability to remove cells when needed, and the ability to use homozygous or heterozygous cells depending on the method.
Advantages of the Ex Vivo Gene Therapy Solutions
- Compared to allogeneic transplantation of hematopoietic cells, ex vivo gene therapy has the ability to allow the reimplantation of autologous cells, which can avoid immune rejection.
- Maintaining the favorable regenerative capacity of stem cells in damaged tissues.
- Increasing the therapeutic potential of allogeneic transplantation through gene transfer.
- Ability to overexpress therapeutic genes in hematopoietic stem cells and their progeny.
We are very innovative in the development phase to achieve each client's individual goals. We are ready to explore the value of ex vivo gene therapy to meet the requirements of novel LSDs treatment strategies. For more information, please feel free to contact us.
Reference
- Biffi A. (2016) Gene therapy for lysosomal storage disorders: a good start[J]. Human molecular genetics. 25(R1): R65-R75.