Mucopolysaccharidoses Treatment with Gene Therapy

By Daniel Walocha ‘19

Gene_Therapy (1)
Figure 1. Gene therapy has the potential to restore normal enzyme levels.

Muscopolysaccharidoses (MPS) is a lysosomal storage disorder which results from a deficiency of lysosomal enzymes. The lack of enzymes causes an accumulation of glycosaminoglycans that can lead to severe symptoms including heart disease, nervous system damage, and skeletal dysplasia. Enzyme replacement therapies, hematopoietic stem cell transplantation, and substrate reduction therapy are short-lived and temporary resolutions that cannot reach a number of key target tissues, such as the brain due to the blood brain barrier. Gene therapy presents a permanent solution to the serious MPS disorder.

Kazuki Sawamoto, Ph.D from the University of Delaware outlines the possibility for an effective gene therapy for MPS. The gene therapy can be in vivo or ex vivo, in which the gene vector is directly delivered in the patient’s cells or the cells are transfected outside of the patient and subsequently reintroduced via transplantation, respectively. Benign viral vector systems, such as the adeno-associated virus (AAV), are usually implemented to spread the gene of interest rapidly throughout the body. Specifically, the AAV can transmit the necessary enzyme through the blood brain barrier by transcytosis. But the difficulty in gene therapy is integrating into the host genome. Without integration, the effect of gene therapy is transient, but with the viruses that can integrate into the host genome, gene transfer can cause tumorigenesis. Integrating a viral promoter near an oncogene could cause excessive and uncontrolled cell growth; similarly, integrating near a tumor suppressor gene could inactivate it. Episomes present a solution to this integration problem since they express a gene without integration, making the AAV the most viable option: allowing for long-term expression, low immunogenicity, and stability.

The AAV vector presents a solution to the most prevalent problem in gene therapy, but upon further inspection, more complications must be considered. The AAV vector has delayed expression in transduced cells, and the AAV vector can only deliver a small amount of exogenous DNA. Future studies must consider these problems to deliver better clinical trial potential.  


  1. K. Sawamoto, et al., Gene therapy for Mucopolysaccharidoses. Molecular Genetics and Metabolism 122, (2017). doi: 10.1016/j.ymgme.2017.12.434.
  2. Image retrieved from:

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