1. Phase 1/2 Open-label Dose-escalation Study of Plasmid DNA Expressing Two Isoforms of Hepatocyte Growth Factor in Patients With Painful Diabetic Peripheral Neuropathy 
Senda Ajroud-Driss, Mark Christiansen, Jeffrey A Allen, John A Kessler 
Molecular Therapy 
Volume 21, Issue 6, Pages (June 2013)
DOI: /mt
Copyright © 2013 The American Society of Gene & Cell Therapy Terms and Conditions

2. Figure 1
Effect of VM202 injection on visual analog scale (VAS) and SF-MPQ in 12 patients separated by cohort. (a) The average VAS scores over time are represented by dose cohorts. The decrease in reported pain occurred in a dose-dependent manner. Notably, at the highest dose, the maximal effect was observed at 6 months follow-up. (b) Although there was no statistically significant reduction among the dose cohorts, a trend of dose responsiveness was observed on short form McGill questionnaire (SF-MPQ) during the study period. Data are expressed as the mean ± SD and analyzed using one-way analysis of variance followed by Dunnett's test or Games-Howell's test. ‡P < 0.05, day 0 versus 6 months or 12 months; †P < 0.05, day 0 versus 2, 3 or 12 months; *P = 0.001, day 0 versus 6 months.
Molecular Therapy  , DOI: ( /mt )
Copyright © 2013 The American Society of Gene & Cell Therapy Terms and Conditions

3. Figure 2
Diagram of the naked DNA designed to express two isoforms of hepatocyte growth (HGF) factor. A hybrid between the genomic and cDNA sequences of HGF was inserted into pCK, an expression vector that is characterized by the presence of the full-length promoter as well as the entire untranslated exon sequences (exon 1 and exon 2) and the intron I sequence from the major immediate-early (IE) region of human cytomegalovirus (HCMV).41 The resulting plasmid, VM202, is 7,377 base pair long. This construct allows the efficient coexpression of both HGF723 and HGF728,7,8 which differ by five amino acids as shown in the figure. HCMV IE promoter (pink arrow, boxes, and wavy line), promoter, and enhancer of the IE gene of the HCMV containing its entire 50-untranslated region upstream from the initiation codon of the IE gene; HGF-X7 (blue boxes and wavy line), genomic-complementary DNA (cDNA) hybrid of the HGF gene by inserting truncated intron 4 into the junction of exons 4 and 5 of HGF cDNA; pA (green box), poly A tract of bovine growth hormone gene; Kan r. (violet box), kanamycin resistance gene; ColE1 (orange box), E coli origin of replication.
Molecular Therapy  , DOI: ( /mt )
Copyright © 2013 The American Society of Gene & Cell Therapy Terms and Conditions