Cystic Fibrosis Gene Therapy Hurdle Overcome
Cold virus delivers sufficient levels of gene to correct mucus transport defect
FRIDAY, July 24 (HealthDay News) -- A virus that normally infects lung cells and causes the common cold has been successfully used to deliver sufficient levels of the gene defective in cystic fibrosis, overcoming a major hurdle to using gene therapy to correct the disease, according to a study published online July 21 in PLoS Biology.
Liqun Zhang, Ph.D., from the University of North Carolina at Chapel Hill, and colleagues engineered a human parainfluenza virus to express the CFTR gene, which is defective in cystic fibrosis, and used the virus to infect human cystic fibrosis ciliated surface airway epithelium to determine whether this could deliver sufficient CFTR to correct the disease.
The researchers found that the engineered virus delivered CFTR to more than 60 percent of cells and increased CFTR expression to about 100-fold over normal levels. This fully corrected the defects in the transport of chloride and sodium ions and restored airway surface liquid volume regulation and mucus transport. Further experiments showed that only 25 percent of cells needed to be infected to restore normal mucus transport, according to the authors.
"Collectively, the studies reported here demonstrate the efficiency of CFTR delivery to human cystic fibrosis ciliated airway epithelium that is sufficient to reverse the cystic fibrosis phenotype of airway surface liquid dehydration and mucostasis," Zhang and colleagues conclude.