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ADENOVIRUS VECTORS: Thixotropic solutions enhance viral-mediated gene

 transfer to airway epithelia

BODY:

       " Adenovirus-mediated gene transfer to airway epithelia

is inefficient in part because its receptor is absent on the apical

surface of the airways. Targeting adenovirus to other receptors,

increasing the viral concentration, and even prolonging the incubation

time with adenovirus vectors can partially overcome the lack of

receptors and facilitate gene transfer. Unfortunately, mucociliary

clearance would prevent prolonged incubation time in vivo, " researchers

in the United States report.

      University of Iowa researcher M.P. Seiler and

colleagues decided to try thixotropic solutions to address this problem.

       " Thixotropic solutions (TS) are gels that upon a

vigorous shearing force reversibly become liquid, " they explained. " We

hypothesized that formulating recombinant adenoviruses in TS would

decrease virus clearance and thus enhance gene transfer to the airway

epithelia. "

      Writing in the American Journal of Respiratory Cell

and Molecular Biology, Seiler and team said they found " clearance of

virus-sized fluorescent beads by human airway epithelia in vitro and by

monkey trachea in vivo was markedly decreased when the beads were

formulated in TS compared with phosphate-buffered saline (PBS).

       " Adenovirus formulated in TS significantly increased

adenovirus-mediated gene transfer of a reporter gene in human airway

epithelia in vitro and in murine airway epithelia in vivo, " they said

(Thixotropic solutions enhance viral-mediated gene transfer to airway

epithelia. American Journal of Respiratory Cell and Molecular Biology,

2002;27(2):133-140).

       " Furthermore, an adenovirus encoding the cystic

fibrosis transmembrane regulator (CFTR) gene (AdCFTR) formulated in TS

was more efficient in correcting the chloride transport defect in cystic

fibrosis airway epithelia than AdCFTR formulated in PBS. "

      The researchers concluded: " These data indicate a

novel strategy to augment the efficiency of gene transfer to the airways

that may be applicable to a number of different gene transfer vectors

and could be of value in gene transfer to cystic fibrosis (CF) airway

epithelia in vivo. "

Becki

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