IEEE Spectrum - North American - March 2016 - 15

is so simple and efficient, any lab can do "We don't really understand why that is," Researchers can also intentionally introit." Traditional genome modification tech- he says. That's where software comes in. duce a piece of new genetic code to the site.
Guide RNAs find their targets in an
niques involve shuttling DNA into cells Algorithms can help researchers design
without knowing where in the genome it their CRISPR tools in a way that is statis- organism's genome by looking for a DNA
segment with a complementary code
will stick. Editing with CRISPR is like plac- tically more likely to succeed.
ing a cursor between two letters in a word
CRISPR systems are equipped with of molecules. The molecules are called
processing document and hitting "delete" two main features: a short strand of pro- bases and are represented by the letor clicking "paste." And the tool can cost grammable genetic code (called a guide ters A (adenine), T (thymine), G (gualess than US $50 to assemble. There are RNA) and a protein (usually an enzyme nine), and C (cytosine) [see illustration,
other genome-editing systems that are called Cas9) that acts as a pair of molecular "Smart Scissors"].
Scientists editing the genome are usuas precise as CRISPR, but they must be scissors. Once the complex is introduced
customized for every use and require far into a cell, the guide RNA ushers Cas9 to ally looking for a segment that controls
more expertise and resources to assemble. a precise location in an organism's DNA a particular function-a gene. Those
As good as CRISPR is compared to its sequence (or genome), sticks to it like Vel- are generally hundreds to thousands
predecessors, the tool doesn't always cro, and lets the Cas9 snip the DNA. The of bases long. Guide RNAs, however, are
work, says Jacob Corn, scientific direc- cell's own machinery then repairs the cut, only about 20 bases long, so scientists
tor at the Innovative Genomics Initiative chewing up a bit of DNA or adding some must choose a complementary 20-base
at the University of California, Berkeley. in the process, thus disrupting the gene. segment within the gene to target. There
are two main constraints to consider:
The target has to be located near a landmark that the molecular scissors can
recognize, and it must be unlike any
The CRISPR system consists of an enzyme capable of chopping DNA and a piece
other 20-base segment anywhere else
of "guide RNA," which places the enzyme at the correct spot in the genome. The
in the genome.
guide RNA is engineered to steer the enzyme to a particular spot in the DNA.

smart scissors

Cas9 enzyme

CRISPR complex

Guide RNA

CRISPR complex
(Cas9 + guide RNA)

DNA base

a
t

g
C

t
a

PAM
sequence
C
g

DNA encodes genes as a sequence of
chemicals (symbolized as A, T, G, and C)
that mate with their chemical complements
(A with T, G with C) to form the rungs of the
molecular helix.

Guide RNA ushers the CRISPR complex to a complementary site in the DNA,
where the enzyme looks for landmarks called protospacer adjacent motifs, or
PAMs. If the complex finds both a DNA match and a PAM, it snips the DNA strand
so that either the gene's sequence will be disrupted or a new piece of DNA can
be inserted at the site.

nEwS

teChnICal IllUStratIon by

Emily Cooper

SPECTRUM.IEEE.ORG

nORTh aMERICan

MaR 2016

http://SPECTRUM.IEEE.ORG

Table of Contents for the Digital Edition of IEEE Spectrum - North American - March 2016