Jianmin Fang

Degradable matrices containing expression plasmid DNA [gene-activated matrices (GAMs)] were implanted into segmental gaps created in the adult rat femur. Implantation of GAMs containing beta-galactosidase or luciferase plasmids led to DNA uptake and functional enzyme expression by repair cells (granulation tissue) growing into the gap. Implantation of a GAM containing either a bone morphogenetic protein-4 plasmid or a plasmid coding for a fragment of parathyroid hormone (amino acids 1-34) resulted in a biological response of new bone filling the gap. Finally, implantation of a two-plasmid GAM encoding bone morphogenetic protein-4 and the parathyroid hormone fragment, which act synergistically in vitro, caused new bone to form faster than with either factor alone. These studies demonstrate for the first time that repair cells (fibroblasts) in bone can be genetically manipulated in vivo. While serving as a useful tool to study the biology of repair fibroblasts and the wound healing response, the GAM technology may also have wide therapeutic utility.

Monoclonal antibody (mAb) delivery by gene transfer in vivo may be an attractive alternative to current mAb therapies for applications that require long-term therapy. This article describes a transfer system that allows inducible high-level expression of unmodified mAbs in vivo. A recombinant adeno-associated viral (rAAV) vector is used that comprises an expression cassette consisting of a dimerizer-regulated promoter that drives expression of the antibody heavy and light chains linked by a 2A self-processing peptide and a furin cleavage site. Following intravenous injection of the rAAV vector, serum mAb levels >1 mg/ml were attained by administration of the inducer, rapamycin. Antibody expression could be rapidly shut off by discontinuing treatment with rapamycin. By optimizing the furin cleavage sequence, this system generated native antibody in vivo, decreasing the likelihood of a host immune response to foreign sequences. In summary, this optimized mAb expression system allows regulated high-level expression of native full-length mAbs in vivo and may offer a new opportunity for delivery of therapeutic mAbs in the clinic. Monoclonal antibody (mAb) delivery by gene transfer in vivo may be an attractive alternative to current mAb therapies for applications that require long-term therapy. This article describes a transfer system that allows inducible high-level expression of unmodified mAbs in vivo. A recombinant adeno-associated viral (rAAV) vector is used that comprises an expression cassette consisting of a dimerizer-regulated promoter that drives expression of the antibody heavy and light chains linked by a 2A self-processing peptide and a furin cleavage site. Following intravenous injection of the rAAV vector, serum mAb levels >1 mg/ml were attained by administration of the inducer, rapamycin. Antibody expression could be rapidly shut off by discontinuing treatment with rapamycin. By optimizing the furin cleavage sequence, this system generated native antibody in vivo, decreasing the likelihood of a host immune response to foreign sequences. In summary, this optimized mAb expression system allows regulated high-level expression of native full-length mAbs in vivo and may offer a new opportunity for delivery of therapeutic mAbs in the clinic.

Aliment Pharmacol Ther 2010; 32: 562–572 Summary Background Dyspepsia and irritable bowel syndrome (IBS) are common in Western populations. Aim To determine the epidemiology of dyspepsia and IBS in China. Methods A representative sample of 18 000 adults from five regions of China were asked to complete the modified Rome II questionnaire; 20% were asked to complete the 36‐item Short Form Health Survey (SF‐36). Participants from Shanghai were invited to provide blood samples and undergo oesophagogastroduodenoscopy. Odds ratios (ORs) and 95% confidence intervals (CIs) were determined using a multivariate logistic regression model. Results The survey was completed by 16 091 individuals (response rate: 89.4%). Overall, 387 participants (2.4%) had dyspepsia and 735 (4.6%) had IBS. All SF‐36 dimension scores were at least five points lower in individuals with than without dyspepsia or IBS ( P ≤ 0.001). In Shanghai, 1030 (32.7%) of the 3153 respondents agreed to endoscopy; neither dyspepsia nor IBS was found to be associated with reflux oesophagitis, peptic ulcer disease or Helicobacter pylori infection. Conclusions Prevalence estimates for dyspepsia and IBS in China are lower than in Western populations. In China, dyspepsia or IBS symptoms are generally not associated with underlying organic disease.