Breakthrough in Gene Therapy
Patrick Auburgh, a pediatric neurologist in Paris and
his colleagues have recently made history by treating 2 patients of X-
linked adrenoleukodystrophy (ALD) with gene therapy.
Currently the only therapy in ALD is bone marrow
transplant. However, these two patients had no compatible donors.
Hematopoetic stem cells were extracted from the patients. The normal gene
which produces the ALD protein was inserted into these cells using an HIV
derived lentivirus. Meanwhile the patients received chemotherapy to ablate
their bone marrow to stop producing stem cells. Then they were infused
with the treated stem cells. Beginning 14 to 16 months after infusion of
the genetically corrected cells, progressive cerebral demyelination
in the two patients stopped.
Viruses have been used for several years to deliver
genetic material into actively dividing cells. This is a problem when
using stem cells since they divide slowly. This was overcome by using the
lentivirus like HIV which can integrate into a cells genome even when it
is not actively replicating. To overcome activating oncogenes, Aurberg
used a modified lentivirus which would not activate any close by genes.
(Science 6 November 2009:326; 818 – 823)
The Nobel Prize for Physiology, 2009
The Nobel Prize for Physiology goes to 3 scientists who
have solved a big question in biology - How DNA is copied in its entirety
during cell division and how progressive degradation inside the cell is
prevented? The answer lies at the end of the chromosome – the telomere and
the enzyme that forms it – the telomerase.
When Elizabeth Blackburn (University of California) was
working on the DNA sequence of a uniciliate organism called Tetrahymena
she found that the ends of the DNA had a repetitive sequence CCCCAA.
Around the same time Jack Szostak (Massachusetts General Hospital, Boston)
found that when a minichromosome was introduced into a cell, it soon got
degraded. The 2 scientists got together and added the CCCCAA sequence to
the end of the minichromosome. Surprisingly, it prevented the degradation
of the chromosome in an entirely different organism like the yeast. Soon
it became clear that telomere DNA is present in all living creatures.
Subsequently Elizabeth’s graduate student, Carol Greider discovered the
telomerase enzyme that extends telomere DNA without missing the very end
portion.
Ongoing work has shown that if the telomere or
telomerase is ineffective, the cell undergoes premature senescence. Hence
there was initially great excitement that the secret of aging lies in the
telomere. However the mechanism of aging is now considered to be much more
complex. But several other genetic disorders including congenital aplastic
anemias have been shown to be due to defective telomerase. The reverse is
also true. For example, cancer cells often have overactive telomerase.
Many clinical trials are now underway on a vaccine against cells with
overactive telomerase. (Scientific American, 5 October 2009).