Real Science and Other Adventures

CRISPR-Cas9 and genome editing

Science Magazine recently announced their Breakthrough of the Year for 2015. It’s CRISPR-Cas9 genome editing.

Genome editing means changing an organism’s genetic instructions by changing its DNA sequence. You could do this for a number of reasons – perhaps to change, add or delete a gene and see what effect that has on the organism – this helps you to learn what the gene does. There are also many genetically modified organisms whose DNA has been changed to make them useful to humans.

The difference between CRISPR-Cas9 and other genome editing methods is that it’s simpler to use and much more precise. This neat video shows how CRISPR-Cas9 genome editing works and discusses how it might be used.

Earlier methods of inserting DNA into a genome are imprecise – the DNA could go in anywhere. It could interrupt another gene, or it could end up next to a gene switch (promoter) that makes it produce the wrong amount of protein. CRISPR-Cas9 gets over this problem. The DNA cut can be made exactly where it’s wanted.

The CRISPR-Cas9 system is a type of bacterial immune system against bacterial viruses. The bacterium makes a piece of guide RNA that matches and binds to a piece of the virus’s DNA by complementary base pairing (U in the RNA pairs with A in the viral DNA, C pairs with G etc). When the Cas9 nuclease notices this DNA-RNA hybrid it cuts it, so the virus can’t reproduce itself.

A nuclease is an enzyme that cuts DNA or RNA. You may have heard of restriction enzymes that cut DNA at specific sequences – these are another type of nuclease. Oh, and CRISPR stands for a phrase that means repeated blocks of bacterial DNA, and the viral DNA is sandwiched between them (Clustered Regularly Interspaced Short Palindromic Repeats). Yes, bacteria edit their own genomes by pasting bits of viral DNA into their genome to give them this special bacterial adaptive immunity.

CRISPR-Cas9 genome editing has a number of possible uses.  Gene therapy has been a dream of medical researchers for a long time. The idea behind it is that a properly functioning gene is added to the genome of someone with a genetic disease. Progress has been slow and there have been problems. Until now the added gene could slot in anywhere in the genome, and some gene therapy trials caused leukaemia when the gene ended up causing an abnormally high rate of cell division.

There’s a big difference between editing germline DNA and somatic DNA. Germline DNA is passed on to the next generation in the gametes, but the DNA in the rest of the body is not passed on. Gene therapy trials have focussed on fixing genetic mistakes in somatic cells. Editing the germline is riskier and more profound because any changes could be passed on to offspring and become permanent. Scientists are already seeking permission to do genome editing experiments on early human embryos. Human embryos used for research are not allowed to grow for more than 14 days in the UK, where this research is proposed.

Do you know of any severe genetic disorders and how devastating they can be? (Check this link for a description of some of them.) Is it ethical to treat someone with a genetic disease by editing their genome? What about editing the genome for other reasons like changing physical features? Should human embryos be genetically modified and then destroyed for research that might help others?

What do you think?

Here’s a TED Talk by Jennifer Doudna, the inventor of CRISPR-cas9 genome editing, where she discusses the ethics of editing human genomes. She and other scientists have called for a ban on using this technique on humans until the ethical and safety issues are considered. She makes the point that HIV has been removed from human cells in the lab using the CRISPR-cas9 system. She also explains the science.

QUESTIONS TO MAKE YOU THINK!

  1. How would the bacteria be able to make a specific “guide RNA” that matches a piece of viral DNA? (Hint – how is RNA made?)
  2. You want to use CRISPR-Cas9 to do some genome editing. Why do you need to design the guide RNA you are going to use?

Answers next time.

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This entry was posted on January 24, 2016 by in DNA tools and techniques, VCE Biology and tagged , , , , , .
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