Horizon eBook - 17

Finding a Signal
Amid the Noise
Nicola McCarthy


| GENengnews.com

new technique has been added to the toolbox of
cell line editing technologies-the RNA-guided
nuclease Cas9, which can be targeted to specific
regions of DNA by single guide RNAs (sgRNAs).
The generation of knockout cells for reagent
testing is much simpler using Cas9-sgRNA than
with ZFNs or TALENs, and also combines well
with homologous recombination-based methods
such as rAAV. The melding of these technologies
has substantially increased our capacity to induce
specific mutations in cell lines1-3 and animal
Tumors are complex entities, and several of
the cellular phenotypes of tumor cells are likely
to be emergent properties (meaning that they

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esearchers have had to come to terms with
the fact that there is unlikely to be a single
wonder drug that will effectively treat all patients
with a specific type of cancer. The race is therefore now on to find ways of understanding drug
sensitivities in specific patient populations.
Many drug discovery projects have focused on
finding inhibitors of dominantly acting oncogenes,
such as tyrosine kinases. Isogenic cell line pairs,
which differ only by a single precisely engineered
modification, can aid patient stratification for
such targeted agents and also help to determine
the mechanisms of resistance that might arise in
patients. Generation of isogenic cell lines is a
specialized process, but in the past 18 months a

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