A new gene-editing technique could lead to more useful animal models of disease, and perhaps one day more effective gene therapy for humans
Genetically modified long-tailed macaques. Credit: Cell, Niu et al.
Like many babies, the wide-eyed twins are cute. The fact that they are macaque monkeys is almost beside the point. What is not beside the point, however, is their genetic heritage. These baby macaques are, as reported inCell, the first primates to have been genetically modified using an extremely precise gene-editing tool based on the so-called CRISPR/Cas system.
Conducted by researchers in China, the new study is significant because it paves the way for the custom development of laboratory monkeys with genetic profiles that are similar to those found in humans with certain medical disorders. Although mice and rats have long been the animals of choice when creating living models of human disease, they have not been very helpful for studying neurological conditions such as autism and Alzheimers disease; the differences between rodent and human brains are just too great.
To be sure, a few other genetically modified monkeys have been born over the past decade and a half, but the methods used to alter their DNA were not as efficient or as easy to use as the CRISPR/Cas technology. The amount of genome engineering in monkeys is pretty small, says George Church, a professor of genetics at Harvard Medical School.So yes, this [paper] is a pretty big deal.
CRISPR stands for clustered regularly interspaced short palindromic repeats and refers to what at first glance appear to be meaningless variations and repeats in the sequence of molecular letters (A, T, C and G) that make up DNA. These CRISPR patterns are found in many bacteria and most archaea (an ancient group of bacteria that is now considered to be different enough from other one-celled organisms to merit is own taxonomic kingdom, along with bacteria, protists, fungi, plants and animals).
First identified in bacteria in 1987, CRISPR elements started being widely used to create genetic engineering tools only in 2013. It took that long to figure out that the patterns actually served a purpose, determine out what that purpose washelping archaea and bacteria to recognize and defend themselves against virusesand then adapt that original function to a new goal.
Basically, biologists learned that certain proteins associated with the CRISPR system (dubbed, straightforwardly enough, CRISPR-associated, or Cas, proteins) act like scissors that cut any strands of DNA they come across. These cutting proteins, in turn, are guided to specific strands of DNA by complementary pieces of RNA (a sister molecule to DNA). The bacteria generate specific guide strands of RNA whenever they encounter a virus that is starting to hijack their cellular machinery. The guide-RNA complements the viral DNA, which is how the Cas proteins know where to cut. The bacteria then keep a copy of the viral DNA in their own genetic sequence between two CRISPR elements for future reference in case a similar virus tries to cause trouble later on.
In the past couple of years researchers have learned how to trick the Cas proteins into targeting and slicing through a sequence of DNA of their own choosing. By developing strands of RNA that precisely complement the part of the DNA molecule that they want to change, investigators can steer the Cas proteins to a predesignated spot and cut out enough genetic material to permanently disrupt the usual expression of the DNA molecule at that location.
In essence, scientists have turned a bacterial self-defense mechanism into an incredibly precise gene-editing tool. By some accounts CRISPR technology has been successfully tried out on 20 different kinds of higher organisms (meaning higher than bacteria) in just the past year or so.
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New Biotech Makes It Much Easier to Genetically Modify Monkeys
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