Monday, May 13, 2019

i-Fect Scores Again

Knock-down of HIF-1a Attenuates Chemo Induced Pain
i-Fect TM is one of our original products. It has enjoyed 14 years of upping transfection percentages both in-vitro and in-vivo.

Here is a new study showing successful use of i-Fect to knock down HIF-1a in-vivo-Taylor Ludman and Ohannes K. Melemedjian. (2019). Bortezomib-induced aerobic glycolysis contributes to chemotherapy-induced painful peripheral neuropathy. Molecular Pain.

Figure 1. (a) Treatment of mice with bortezomib (Bor) for five days augmented HIF1A expression in L4-6 DRGs (*P ¼ 0.0412, five mice/ group) relative to the vehicle-treated group. (b) A schematic depicting the site of the intrathecal (IT) siRNA injection. The siRNA was administered between the L4 and L5 vertebrae which is around 17 mm rostral to the spinal cord (SC) section innervated by the L4-6 DRGs. (c) IT injection of siRNA (1 mg in 5 ml) that targets HIF1A (siRNA) but not control siRNA (Cont), for two consecutive days, significantly reduced the levels of HIF1A in L4-6 DRGs. (***P=0.0006, five mice/group). (d) IT siRNA did not affect HIF1A levels in L4-6 spinal cord (five mice/group). (e) After determining baseline withdrawal thresholds using von Frey filaments, male ICR mice received IP injection of vehicle or bortezomib (black arrows) and IT siRNA (blue arrows). The withdrawal thresholds were measured on days 7 to 14. IT HIF1A siRNA prevented the development of bortezomib-induced neuropathic pain. (****P less than 0.0001, five mice/group). DRG: dorsal rootganglia; HIF1A: hypoxia-inducible factor 1 alpha; IT: intrathecal; IP: intraperitoneal; siRNA: small interfering RNA.

This study is the first to demonstrate that the stabilization of HIF1A expression underpins the development of bortezomib-induced neuropathic pain. Crucially, these findings reveal that the initiation and maintenance of bortezomib-induced neuropathic pain are regulated by distinct mechanisms.

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