Dr. Zhilong Jiang from Drexel University is going to give us a talk about "Lentiviral Vector in Gene Therapy for Spinal Cord Injury" at 6:30 PM next Friday.
Everyone is welcome to join us and to ask questions. Snacks will be provided.
The talk will be held at CRB 302, 6:30 PM. Abstract
Lentiviral vector (Lv) is widely used HIV-based RNA vector for gene transfer, due to its high transduction efficiency into dividing and non-dividing cells, and integration into cell genomes for better gene duration in infected cells. Most importantly, lentiviral vector has deleted of all viral genomes, thus has very lower immune responses than other vector after administration in vivo. Therefore lentiviral vector has much more advantage over other gene transfer vectors (adenoviral vector, HSV vector), promoting long-term gene expression and less immune response in vivo. Our facility have produced several high quality of lentiviral vectors encoding a variety of genes including brain-derived neurotrophic factor (BDNF) and Neurotrophin-3 (NT-3), IL-10, FoxP3, CCR5 and CCR7, etc. The studies in vivo have confirmed their beneficial effects on injured spinal cord recovery.
Spinal cord injury is very common neurological disorder, mostly due to car accident with incidence of 1/20,000 Americans, characterized by neuron loss and destruction of signal transduction pathway between brain cortex and four limbs, ultimately cause paralysis and sensation loss. Re-establishing the connection in the injured sites, by promoting neuron growth and regeneration is essential to functional recovery. Our studies demonstrate that brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) provide neuroprotection and promote axon growth after transplantation into injured spinal cord. First, we infected fibroblasts, adipocyte-derived stromal cells (Ad-MSC) or neuron stem cells (NSC) with Lv BDNF/GFP, Lv NT-3/GFP or Lv-GFP (control), expanded the infected cells for up to 2 weeks. The expression of BDNA and NT-3 remain remained high, up to 80% of 3-day post infection, the gene modified cells expanded for at least 20 times, thus expansion after infection protocol provided enough cells for cell transplantation without compromise of therapeutic gene expression level. In vitro and in vivo functional studies showed that BDNF and NT-3 produced from modified cells facilitated axonal growth in a chick dorsal root ganglion (DRG) and promoted regeneration of axons into injured sites, form synapses and connections with other axons in grafts, thus over-expression of BDNF and NT-3 in injured spinal cord might be promising strategy in gene therapy of spinal cord injury.
