ArticleMolecular genetics and metabolism reports2016
Elements of lentiviral vector design toward gene therapy for treating mucopolysaccharidosis I.
Article in Molecular genetics and metabolism reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- Normothermic perfusion of human livers for profiling lentiviral vector pharmacokinetics and transduction.Molecular therapy. Advances · 2026Article
- Identification of a novel fusion Iduronidase with improved activity in the cardiovascular system.Molecular genetics and metabolism reports · 2022Article
- Regulation of Molecular Targets in Osteosarcoma Treatment.International journal of molecular sciences · 2022Review
- Promoter considerations in the design of lentiviral vectors for use in treating lysosomal storage diseases.Molecular therapy. Methods & clinical development · 2022Review
- Article
- A Highly Efficacious PS Gene Editing System Corrects Metabolic and Neurological Complications of Mucopolysaccharidosis Type I.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Pre-clinical Mouse Models of Neurodegenerative Lysosomal Storage Diseases.Frontiers in molecular biosciences · 2020Review
- Effects of gene therapy on cardiovascular symptoms of lysosomal storage diseases.Genetics and molecular biology · 2019Article
- Long Noncoding RNA lncMUMA Reverses Established Skeletal Muscle Atrophy following Mechanical Unloading.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- A newly identified lncRNA MAR1 acts as a miR-487b sponge to promote skeletal muscle differentiation and regeneration.Journal of cachexia, sarcopenia and muscle · 2018Article
- RTB lectin-mediated delivery of lysosomal α-l-iduronidase mitigates disease manifestations systemically including the central nervous system.Molecular genetics and metabolism · 2018Article
- Skeletal Dysplasias: Growing Therapy for Growing Bones.Frontiers in pharmacology · 2017Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Mucopolysaccharidosis type I (MPS I) is a lysosomal disease caused by α-l-iduronidase (IDUA) deficiency and accumulation of glycosaminoglycans (GAG). Lentiviral vector encoding correct IDUA cDNA could be used for treating MPS I. To optimize the lentiviral vector design, 9 constructs were designed by combinations of various promoters, enhancers, and codon optimization. After in vitro transfection into 293FT cells, 5 constructs achieved the highest IDUA activities (5613 to 7358 nmol/h/mg protein). These 5 candidate vectors were then tested by injection (1 × 10(7) TU/g) into neonatal MPS I mice. After 30 days, one vector, CCEoIDW, achieved the highest IDUA levels: 2.6% of wildtype levels in the brain, 9.9% in the heart, 200% in the liver and 257% in the spleen. CCEoIDW achieved the most significant GAG reduction: down 49% in the brain, 98% in the heart, 100% in the liver and 95% in the spleen. Further, CCEoIDW had the lowest transgene frequency, especially in the gonads (0.03 ± 0.01 copies/100 cells), reducing the risk of insertional mutagenesis and germ-line transmission. Therefore, CCEoIDW is selected as the optimal lentiviral vector for treating MPS I disease and will be applied in large animal preclinical studies. Further, taken both in vitro and in vivo comparisons together, codon optimization, use of EF-1α promoter and woodchuck hepatitis virus posttranscriptional response element (WPRE) could enhance transgene expression. These results provided a better understanding of factors contributing efficient transgene expression in lentiviral gene therapies.
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Registered trials
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