Lentiviral Vector Development for Wiskott-Aldrich Syndrome
Wiskott-Aldrich syndrome (WAS) is a life-threatening immunodeficiency caused by mutations within the WAS gene. Lentiviral vector (LV)-based gene therapy of WAS is a promising alternative. With Ph.D. level scientists and extensive experience in LV development, Creative Biolabs is dedicated to serving every unique need of our clients in LV development for WAS by providing customized services.
The Background of WAS
WAS is a rare X-linked primary immunodeficiency that results from the loss of WAS protein (WASp). WASp involves in signal transduction pathways that activate the actin cytoskeleton downstream of multiple cell surface receptors, including the B and T cell antigen receptors. And WAS is characterized by micro-thrombocytopenia, recurrent infections, eczema. This complex disease is also associated with a high incidence of autoimmunity and lymphoid malignancies. More and more attentions are paid to WAS not only because it highlights the rich cellular-biology and systems-biology but also because it is a candidate for hematopoietic stem cell gene therapy indication.
Gene Therapy of WAS
Although the phenotype of WAS can be alleviated by hematopoietic stem cell transplantation (HSCT), the success rate of this therapy is variable, which depends on the patient's age, donor compatibility, conditioning regimen, and the extent of reconstitution. Since the phenotype of WAS deficiency impacts only hematopoietic cells, gene therapy is a possible alternative. The gene therapy of WAS represents a new challenge compared to other immune deficiencies. WASp can be stably integrated into the chromatin of autologous hematopoietic stem cells (HSCs) using viral-based gene delivery. The use of self-inactivating LVs for gene transfer is one critical improvement, combining a safer integration profile with the ability to select internal promoters that optimize transgene expression and safety.
LV Development for WAS at Creative Biolabs
Scientists at Creative Biolabs have developed an LV that combines a chromatin insulator upstream of a viral promoter to drive WASp expression. Used as a gene therapeutic, this efficient vector resulted in stable WASp+ cells in all hematopoietic lineages and rescue of T and B cell defects with a low number of viral integrations and without insertional mutagenesis. Our results demonstrate that this promoter safely and efficiently reconstitutes WASp expression and can be potentially used for future WAS therapy.
Key Advantages of Our Service:
- Reduced impact of LV transduction on hematopoiesis
- Safety design of LV vector
- Absence of hematopoietic toxicity
- Purified product under good manufacturing practices (GMP)
- Best after-sale service
With years of experience in safety design and high-titer production of LV, Creative Biolabs has gained significant knowledge in LV development for WAS. We are more than happy to share our experience and help our customers with this important step in LV-based gene therapy for WAS. Please contact us for more information and a detailed quote.
