Researchers Produce a New Viral Vector with the Potential to Treat Cystic Fibrosis
Cystic fibrosis symptoms affect many systems of the body: Image by Mikael Haggstrom.
Cystic Fibrosis (CF) is a very common genetic disorder that currently has no cure and few effective treatments. The disease is caused by a defective recessive gene, which was identified in 1989. According to the Cystic Fibrosis Foundation, 1 in 31 Americans carry the CF gene, which is more common in Caucasians of European descent, but can appear in any race or nationality.
The presentation of the disorder includes thick mucous, persistent lung infections, breathing difficulty, digestive disease, pancreatic insufficiency, and even the need for lung transplants in critical cases. Research into gene therapy as a treatment for CF has been ongoing for over two decades, but a breakthrough still remains elusive. However, in June 2011 the UK Cystic Fibrosis Gene Therapy Consortium, composed of scientists from Imperial College, London, University of Oxford and University of Edinburgh, received two Medical Futures Innovation Awards for their ‘Lentiviral Gene Therapy Programme for Cystic Fibrosis’, which holds great promise for effective long-term treatment of the disease.
Location of the gene on Chromosome 7. Image by Ensemble
The Cystic Fibrosis Gene: The ΔF508 Mutation
The majority of CF cases are caused by a mutation located in the mid-region of the long-arm of chromosome 7, which is known as the CFTR gene (cystic fibrosis transmembrane conductance regulator). The gene is essential for proper chloride ion transport and a mutation disrupts the delicate balance between sodium and chloride ions. This ionic imbalance results in unnaturally thick mucous, which becomes trapped in the lungs of CF patients.
According to the Human Genome Database, ’70 percent of mutations observed in CF patients result from deletion of three base pairs in CFTR’s nucleotide sequence‘. This deletion causes loss of the amino acid phenylalanine located at position 508. Thus, the mutation is termed ΔF508, where F represents phenylalanine and 508 is the codon number. The ΔF508 mutation is the most common cause of CF, but hundreds of other mutations are also possible causes of the disorder. Almost all other mutations are missense or nonsense mutations and usually derive from single base changes.
Gene Therapy: Mechanism – Viral Vectors
Gene therapy is used to correct defective genes in a number of genetic disorders, usually by insertion of a normal gene into the patient’s genome via a viral vector or sometimes by non-viral methods. Viral vectors, created from retroviruses or adenoviruses, are traditionally the most common method of gene therapy. The viruses used to carry the normal genes have been genetically altered in the lab both to effectively carry human genes and to be non-toxic to the patient.
Once the vector is distributed to the patient, it transfers the normal human gene into the patient’s genome, which, ideally, corrects the function of the abnormal gene and resolves the disease. The process of creating a viral vector in the lab is quite complicated, but the University of Utah’s Genetic Science Learning Center has produced an informative guide to the basics of vectors.
Click to Read Page Two: Gene Therapy in Cystic Fibrosis
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