PubMed Health⌕ Search

Biomedical subjects

C Kitson

Publications and source records attributed to C Kitson.

7 recordsLinked to original sources
PubMed2001

Mucus altering agents as adjuncts for nonviral gene transfer to airway epithelium.

Nonviral vectors have been shown to be a safe and valid alternative to recombinant viruses for gene therapy of cystic fibrosis (CF). Nevertheless, gene transfer efficiency needs to be increased before clinical efficacy is likely in man. One barrier to increased efficacy is normal airway mucus. Using an ex vivo model of sheep tracheal epithelium, we show that this barrier can, in part, be overcome by treatment with the mucolytic agents, Nacystelyn or N-acetylcysteine using either a cationic lipid or a cationic polymer as the gene transfer agent. Further, in vivo application of either Nacystelyn or the anticholinergic glycopyrrolate, both clinically used agents, resulted in increased reporter gene expression in the mouse lung, but no significant correction of the bioelectric defect in CF null mice. These results, whilst unlikely to be sufficient in themselves to achieve clinically relevant gene therapy, may be a further useful step in the attainment of this goal.

Acetylcysteine↗
PubMed2000

Efficient gene transfer to airway epithelium using recombinant Sendai virus.

Clinical studies of gene therapy for cystic fibrosis (CF) suggest that the key problem is the efficiency of gene transfer to the airway epithelium. The availability of relevant vector receptors, the transient contact time between vector and epithelium, and the barrier function of airway mucus contribute significantly to this problem. We have recently developed recombinant Sendai virus (SeV) as a new gene transfer agent. Here we show that SeV produces efficient transfection throughout the respiratory tract of both mice and ferrets in vivo, as well as in freshly obtained human nasal epithelial cells in vitro. Gene transfer efficiency was several log orders greater than with cationic liposomes or adenovirus. Even very brief contact time was sufficient to produce this effect, and levels of expression were not significantly reduced by airway mucus. Our investigations suggest that SeV may provide a useful new vector for airway gene transfer.

Adenoviridae↗
PubMed2000

Gene therapy for cystic fibrosis.

The gene for cystic fibrosis was identified in 1989 and this together with the emerging technology of gene therapy heralded a new dawn for the treatment of genetic disease. The initial optimism however gave way to the realisation that gene therapy for cystic fibrosis was unlikely to be straightforward. The lung was considered an ideal organ to target due to ease of access, but subsequent research has shown that the airway surface provides an efficient barrier to topically applied gene transfer agents. A number of Phase I clinical safety trials were carried out through the 1990s and provided proof of concept evidence that delivery of DNA by either viral or non-viral means was safe though not clinically efficacious. Current research is now focusing more on the barriers faced by delivery agents, with the aim that more efficient gene delivery will lead to a gene therapeutic for cystic fibrosis.

Cystic Fibrosis↗
PubMed1999

The extra- and intracellular barriers to lipid and adenovirus-mediated pulmonary gene transfer in native sheep airway epithelium.

Gene transfer to the respiratory epithelium is currently suboptimal and may be helped by the identification of limiting biological barriers. We have, therefore, developed an ex vivo model which retains many of the characteristics of in vivo native airways including mucociliary clearance, mucus coverage and an intact cellular structure. Using this model we have demonstrated several barriers to gene transfer. Liposome-mediated gene transfer was inhibited by normal mucus, with removal of this layer increasing expression approximately 25-fold. In addition both liposome and adenovirus were inhibited by CF sputum. The apical membrane represented a significant barrier to both agents. Adenovirus-mediated expression could be significantly augmented by increasing contact time or by pre-treatment of tissues with a nominally calcium-free medium. The presence of these extracellular and plasma membrane barriers appeared to be the key parameters responsible for the approximately three log difference in gene expression found in vitro compared with our ex vivo model. Cytoskeletal elements and the cell cycle also influenced in vitro gene transfer, and represent further barriers which need to be overcome.

Adenoviridae↗
PubMedDate not supplied

Trauma outreach education: assessing the needs of rural health care providers.

Trauma centers find it a challenge to provide appropriate, cost-effective outreach education. A needs assessment of rural health care providers was conducted to determine "what," "how," and "where" was preferred. The results showed that multidisciplinary rural providers were consistent with their preferences, that they considered case reviews the most effective method, that weekday evenings were the most convenient time, and that their lack of experience was their greatest barrier to learning.

Education, Nursing, Continuing↗