Lipoprotein Lipase Deficiency (LPLD)

Adeno-associated virus (AAV) is a versatile viral vector technology that can be engineered for gene therapy applications. Recombinant AAV vectors containing DNA sequences of interest have proven to be one of the safest strategies for gene therapies of hereditary diseases. Based on our experienced team and elaborately technical platforms, Creative Biolabs provides customers around the world with comprehensive AAV vector design services to accelerate their project progress.

Introduction of Lipoprotein Lipase Deficiency

Lipoprotein lipase deficiency (LPLD) is an autosomal recessive disorder caused by loss-of-function mutations in the LPL gene, which is located on chromosome 8p22 and comprises 10 exons. To date, more than 70 LPL gene mutations have been described, most of them associated with loss of catalytic function. The LPL gene encodes the enzyme, lipoprotein lipase (LPL), which has multiple key functions in the catabolism of triglyceride (TG)-rich lipoproteins, chylomicrons (CM) and very-low-density lipoproteins (VLDL). The skeletal muscle, fat tissue, and heart muscle tissue are important sites of LPL production. LPLD is characterized by extreme accumulation of CM and TG in the plasma, hyperchylomicronemia and severe hypertriglyceridemia, which in turn, are associated with an increased risk of clinical complications. Signs and symptoms include hepatosplenomegaly, eruptive xanthomas, severe abdominal pain, peripheral neuropathy and an increased risk of cardiometabolic complications. At present, no drugs are available to effectively modulate the course of the illness. Given the lack of an effective treatment for LPLD, gene replacement therapy provides a new approach to LPLD. One such approach is based on the direct administration of a functional LPL gene variant into the muscle tissue of patients with LPLD caused by loss-of-function mutations in the LPL gene.

AAVs Vector in LPLD Gene Therapy

Lipoprotein Lipase Deficiency (LPLD) - Creative Biolabs

AAV is a nonpathogenic virus that has been safely administered to humans in numerous clinical trials. After a single intramuscular administration of recombinant AAV vector particles, long-term transgene protein expression has been reported in preclinical studies. Given the established safety profile and persistent expression, the AAV vector is selected as a gene therapy vector to deliver the therapeutic gene for patients with LPLD. Studies have shown that biologically active LPL can be produced in muscle by AAV type 1-mediated gene transfer without tissue-specific regulation of the transgene. The human LPL gene variant LPLˢ⁴⁴⁷ˣ, a gain-of-function allele associated with lower plasma TG levels, is selected as the candidate for gene therapy of LPLD patients. Intramuscular administration of AAV1-LPLˢ⁴⁴⁷ˣ has been shown to result in the resolution of chylomicronemia and a life-long reduction in plasma TG concentrations. Nowadays, this method has been approved in the EU for use in adult patients with confirmed LPLD.

Services

Currently, AAV as a delivery vehicle shows great potential in gene therapy for LPLD. Creative Biolabs provides high-quality AAV vector design services for gene therapy of hereditary diseases including LPLD. We have a highly efficient AAV vector expression platform that can stably express LPL gene mutants in the long-term and achieve efficient gene delivery.

Alongside our AAV vector design service for gene therapy, we also provide:

  • AAV vector purification service
  • AAV vector titration service
  • Toxicity and safety determination of AAV vector
  • Other services

For more details, please contact us and we will be happy to help you.

For research use only. Not intended for any clinical use.