Cystic fibrosis is caused by mutations in the CFTR gene which codes for a chloride channel protein. This leads to thick, sticky mucus production throughout the body. The mucus clogs the lungs and pancreas, causing infections and poor digestion. Current treatments only manage symptoms; gene therapy aims to add a functional CFTR gene to lung cells to thin the mucus. However, delivering the gene faces challenges of immune responses, inefficient vectors, and short-term effects. A cure would require altering every cell, which is currently impossible.

1. Cystic Fibrosis (CF)
• Causes
– Several different alleles of a key gene coding for a
transmembrane protein that transports chloride ions
through cell surface membranes (cystic fibrosis
transmembrane regulator, CFTR)
– Inheritance is autosomal (NOT sex-linked) and
recessive – located on chromosome 7
– CF alleles originate by mutation of the CFTR protein,
but can be inherited through many generations
– Individuals with a single copy of such an allele are
heterozygous and do not have the condition (10
million carriers worldwide)
– To have CF, it is necessary to be homozygous for CF
alleles
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4. • Effects of CF
– Reduced chloride transport through cell membranes
leads to production of thick, sticky mucus that affects
lungs, pancreas and reproductive organs
– The mucus remains in the lungs leading to wheezing
and repeated infections (removed by physiotherapy)
– Mucus may block pancreatic duct, compromising
digestion and nutrition and also causing build-up of
protease in the pancreas, damaging the pancreatic
tissue
– Mucus may block sperm ducts (male infertility) and
may slow the progress of eggs and sperm through the
oviducts (reducing female fertility)
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6. Progress towards treating Cystic
Fibrosis with gene technology
• Current treatments deal with the symptoms rather than
the causes
• Research continues to try and develop techniques for
adding functional copies of the CFTR gene to the cells of
people with CF
• It is thought that if even a proportion of lung cells could
be given a working copy of the gene, this would thin the
mucus sufficiently to allow the cilia to operate normally
• Approach trialed is to remove cells from body, add
working copies of the gene and put the cells back
• The working copies of the gene integrate themselves into
random positions in the genome of the treated cells
(repetition and cancer)
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7. • A vector must be used to deliver the DNA
containing the functional CFTR gene into the
lung cells
– Viral delivery systems
• Adenoviruses (group of viruses that infect the membranes of
the respiratory tract, eyes, intestines, and urinary tract) can
be used/viruses which infect lungs
• Virulence removed and genetically engineered to carry
functional human CFTR gene
• Either injection with genetically engineered viruses or inhale
from an aerosol directly into the lungs
– Non-viral delivery systems
• Creation of a lipid sphere or liposome containing DNA
• DNA can be compressed into a very small volume which
may directly enter cells
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10. • There is not yet a successful example of
treatment of CF by gene therapy because:
– Current viral vectors have been found to stimulate
allergic or other immune responses
– Current liposome vectors have proved inefficient at
delivering genes into cells
– The effect of the therapy on chloride ion transport has
lasted only a few days
• A cure would require every one of the 50 x 10 13
cells in the body to be altered, which is not
currently thought to be technically possible and
would raise significant further ethical issues
• To enable people with CF to have children would
require germ-line gene therapy – changes are
made to human gamete cells that are inherited
by the next generation
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11. • http://www.machinegraphics.com/animation/an
• http://presenter.multicastmedia.com/links/CFF
• http://learn.genetics.utah.edu/units/genetherap
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