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.
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.
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 for both ivf and Surrogacy
“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.
