Monday, April 13, 2009

No Couch Needed: Gene Therapy

The completion of the Human Genome Project in 2004, along with the
sequencing of nonhuman genomes, has spawned an incredible revolution
in the understanding of genetics. Simultaneously, geneticists have raced to
develop medicines to treat and cure diseases caused by genes gone awry.
Gene therapy, treatment that gets at the direct cause of genetic disorders,
is sometimes touted as the magic bullet, the cure-all for inherited diseases
(see Chapter 13 for a partial list) and cancer (see Chapter 14). Gene therapy
may even provide a way to block the genes of pathogens such as the virus
that causes AIDS, providing reliable treatments for illnesses that currently
have none.
Unfortunately, the shining promise of gene therapy has been hampered by a
host of factors including finding the right way to supply the medicine to
patients without causing new or worse problems than the ones being treated.
In this chapter, you examine the progress and perils of gene therapy.

Curing Genetic Disease

Take a glance back through for proof that your health and
genetics are inextricably linked. Not only do mutations cause disorders that
are passed from generation to generation, but mutations acquired during
your lifetime can have unwanted consequences such as cancer. And your
own genes aren’t the only ones that cause complications — the genes carried
by bacteria, parasites, and viruses lend a hand in spreading disease and
dismay worldwide.

Curing Genetic Disease

Take a glance back through Part III of this book for proof that your health and
genetics are inextricably linked. Not only do mutations cause disorders that
are passed from generation to generation, but mutations acquired during
your lifetime can have unwanted consequences such as cancer. And your
own genes aren’t the only ones that cause complications — the genes carried
by bacteria, parasites, and viruses lend a hand in spreading disease and
dismay worldwide.

Finding Vehicles to Get Genes to Work

The first step in successful gene therapy is designing the right delivery system
to introduce a new gene or shut down an unwanted one. The delivery
system for gene therapy is called a vector. A perfect vector
 Must be innocuous so that the recipient’s immune system doesn’t reject
or fight the vector.
 Must be easy to manufacture in large quantities. Just one treatment may
require over 10 billion copies of the vector because you need one delivery
vehicle for each and every cell in the affected organ.
 Must be targeted for a specific tissue. Gene expression is tissue-specific
(see Chapter 10 for details), so the vector has to be tissue-specific, too.
 Must be capable of integrating its genetic payload into each cell of the
target organ so that new copies of each cell generated later on by mitosis
contain the gene therapy payload.

viruses are the favored vector

Currently, viruses are the favored vector. Most gene therapies aim to put a
new gene into the patient’s genome, so it’s pretty easy to understand why
viruses are appealing candidates for vectorhood — this gene-sharing action
is almost precisely what viruses do naturally.

virus latches onto a cell

When a virus latches onto a cell that isn’t somehow protected from the virus,
the virus hijacks all that cell’s activities for the sole purpose of making more
viruses. Viruses reproduce this way because they aren’t really alive and have
no moving parts of their own to accomplish reproduction. Part of the virus’s
attack strategy involves integrating virus DNA into the host genome in order
to execute viral gene expression. The problem is that when a virus is good at
attacking a cell, it causes an infection that the patient’s immune system
fights. So the trick to using a virus as a vector is taming it.

Gentling a virus for use as a vector

Gentling a virus for use as a vector usually involves deleting most of its genes.
These deletions effectively rob the virus of almost all its own DNA, leaving only
a few bits. These remaining pieces are primarily the parts normally used by the
virus for getting its DNA into the host.