Exclusive: 'Jaw-dropping' breakthrough hailed as landmark
in fight against hereditary diseases as Crispr technique heralds genetic
revolution
Development
to revolutionise study and treatment of a range of diseases from cancer,
incurable viruses such as HIV to inherited genetic disorders such as
sickle-cell anaemia, Huntington’s disease and Down syndrome
SCIENCE EDITOR
Wednesday 06 November 2013
A breakthrough in genetics – described as “jaw-dropping” by one
Nobel scientist – has created intense excitement among DNA experts around the
world who believe the discovery will transform their ability to edit the
genomes of all living organisms, including humans.
The development has been
hailed as a milestone in medical science because it promises to revolutionise
the study and treatment of a range of diseases, from cancer and incurable
viruses to inherited genetic disorders such as sickle-cell anaemia and Down syndrome.
For the first time, scientists are
able to engineer any part of the human genome with extreme precision using a
revolutionary new technique called Crispr, which has been likened to editing
the individual letters on any chosen page of an encyclopedia without creating
spelling mistakes. The landmark development means it is now possible to make
the most accurate and detailed alterations to any specific position on the DNA
of the 23 pairs of human chromosomes without introducing unintended mutations
or flaws, scientists said.
The technique is so accurate that
scientists believe it will soon be used in gene-therapy trials on humans to
treat incurable viruses such as HIV or currently untreatable genetic disorders
such as Huntington’s disease. It might also be used controversially to correct
gene defects in human IVF embryos, scientists said.
Until now, gene therapy has had
largely to rely on highly inaccurate methods of editing the genome, often
involving modified viruses that insert DNA at random into the genome –
considered too risky for many patients.
The new method, however,
transforms genetic engineering because it is simple and easy to edit any
desired part of the DNA molecule, right down to the individual chemical
building-blocks or nucleotides that make up the genetic alphabet, researchers
said.
“Crispr is absolutely huge. It’s
incredibly powerful and it has many applications, from agriculture to potential
gene therapy in humans,” said Craig Mello of the University of Massachusetts
Medical School, who shared the 2006 Nobel Prize for medicine for a previous
genetic discovery called RNA interference.
“This is really a triumph of basic
science and in many ways it’s better than RNA interference. It’s a tremendous
breakthrough with huge implications for molecular genetics. It’s a real
game-changer,” Professor Mello told The
Independent.
“It’s one of those things that you
have to see to believe. I read the scientific papers like everyone else but
when I saw it working in my own lab, my jaw dropped. A total novice in my lab
got it to work,” Professor Mello said.
In addition to engineering the
genes of plants and animals, which could accelerate the development of GM crops
and livestock, the Crispr technique dramatically “lowers the threshold” for
carrying out “germline” gene therapy on human IVF embryos, Professor Mello
added.
Germline gene therapy on sperm, eggs or embryos to eliminate
inherited diseases alters the DNA of all subsequent generations, but fears over
its safety, and the prospect of so-called “designer babies”, has led to it
being made illegal in Britain and many other countries.
The new gene-editing technique
could address many of the safety concerns because it is so accurate. Some
scientists now believe it is only a matter of time before IVF doctors suggest
that it could be used to eliminate genetic diseases from affected families by
changing an embryo’s DNA before implanting it into the womb.
“If this new technique succeeds in
allowing perfectly targeted correction of abnormal genes, eliminating safety
concerns, then the exciting prospect is that treatments could be developed and
applied to the germline, ridding families and all their descendants of
devastating inherited disorders,” said Dagan Wells, an IVF scientist at Oxford
University.
“It would be difficult to argue
against using it if it can be shown to be as safe, reliable and effective as it
appears to be. Who would condemn a child to terrible suffering and perhaps an
early death when a therapy exists, capable of repairing the problem?” Dr Wells
said.
The Crispr process was first
identified as a natural immune defence used by bacteria against invading
viruses. Last year, however, scientists led by Jennifer Doudna at the
University of California, Berkeley, published a seminal study showing that
Crispr can be used to target any region of a genome with extreme precision with
the aid of a DNA-cutting enzyme called CAS9.
Since then, several teams of
scientists showed that the Crispr-CAS9 system used by Professor Doudna could be
adapted to work on a range of life forms, from plants and nematode worms to
fruit flies and laboratory mice.
Earlier this year, several teams
of scientists demonstrated that it can also be used accurately to engineer the
DNA of mouse embryos and even human stem cells grown in culture. Geneticists
were astounded by how easy, accurate and effective it is at altering the
genetic code of any life form – and they immediately realised the therapeutic
potential for medicine.
“The efficiency and ease of use is
completely unprecedented. I’m jumping out of my skin with excitement,” said
George Church, a geneticist at Harvard University who led one of the teams that
used Crispr to edit the human genome for the first time.
“The new technology should permit
alterations of serious genetic disorders. This could be done, in principle, at
any stage of development from sperm and egg cells and IVF embryos up to the
irreversible stages of the disease,” Professor Church said.
David Adams, a DNA scientist at
the Wellcome Trust Sanger Institute in Cambridge, said that the technique has
the potential to transform the way scientists are able to manipulate the genes
of all living organisms, especially patients with inherited diseases, cancer or
lifelong HIV infection.
“This is the first time we’ve been
able to edit the genome efficiently and precisely and at a scale that means
individual patient mutations can be corrected,” Dr Adams said.
“There have been other
technologies for editing the genome but they all leave a ‘scar’ behind or
foreign DNA in the genome. This leaves no scars behind and you can change the
individual nucleotides of DNA – the ‘letters’ of the genetic textbook – without
any other unwanted changes,” he said.
Timeline: Landmarks in DNA science
Restriction
enzymes: allowed
scientists to cut the DNA molecule at or near a recognised genetic sequence.
The enzymes work well in microbes but are more difficult to target in the more
complex genomes of plants and animals. Their discovery in the 1970s opened the
way for the age of genetic engineering, from GM crops to GM animals, and led to
the 1978 Nobel Prize for medicine.
Polymerase
chain reaction (PCR): a technique
developed in 1983 by Kary Mullis (below, credit: Getty) in California allowed
scientists to amplify the smallest amounts of DNA – down to a single molecule –
to virtually unlimited quantities. It quickly became a standard technique,
especially in forensic science, where it is used routinely in analysing the
smallest tissue samples left at crime scenes. Many historical crimes have since
been solved with the help of the PCR test. Mullis won the Nobel Prize for
chemistry in 1993.
RNA
interference: scientists
working on the changing colour of petunia plants first noticed this phenomenon,
which was later shown to involve RNA, a molecular cousin to DNA. In 1998, Craig
Mello and Andrew Fire in the US demonstrated the phenomenon on nematode worms,
showing that small strands of RNA could be used to turn down the activity of
genes, rather like a dimmer switch. They shared the 2006 Nobel Prize for
physiology or medicine for the discovery.
Zinc
fingers: complex
proteins called zinc fingers, first used on mice in 1994, can cut DNA at
selected sites in the genome, with the help of enzymes. Another DNA-cutting
technique called Talens can do something similar. But both are cumbersome to
use and difficult to operate in practice – unlike the Crispr technique.
Click HERE to see how the Crispr system derived
from bacteria works on human cells to correct genetic defects
Video by
Janet Iwasa
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