A few months ago I saw Dr Lissa Herron, one of the Roslin scientists involved with Eggcellent Proteins, speak at the launch of Roslin Technologies. I heard that her business proposition was to create “chicken bioreactors” by integrating DNA coding for certain pharmaceutical proteins into the chicken genome. The proteins are only expressed in the egg white and easily extracted. This method gives higher yields of protein compared with other protein expression systems.
Manipulating a genome in this manner is a powerful tool, and technology is now available to target foreign DNA to specific locations in a given genome. The CRISPR-Cas9 system, now widely used in research, allows scientists to edit parts of the genome by removing, adding or altering sections of the DNA sequence.
CRISPR–Cas9 stands for “clusters regularly interspaced palindromic repeats” found naturally in some bacteria. Bacteria use it as a “gene editing” technique to defend against invading organisms such as viruses. In a palindromic repeat the sequence of nucleotides is the same in both directions. Each repetition is followed by short segments of spacer DNA from previous exposures to foreign DNA. The palindromic DNA sequences provide the bacteria with a “memory” of viruses which the bacteria have been exposed to. The bacteria use the CRISPR sequences to recognise the same viruses that subsequently invade the bacteria, and the viral target DNA will then be cut up with the bacteria's CRISPR-associated (CAS) enzymes.
Scientists have been able to harness this method to cut out, replace, or add parts to a DNA sequence, making the technique a precise form of genetic manipulation.
However the technology has attracted controversy, with a contentious legal battle in the US only recently settled (and perhaps only for the moment) as to who owns the CRISPR-Cas9 patent.
The Patent Trial and Appeal Board ruled in February that the Broad Institute of MIT and Harvard rightfully owns its CRISPR-Cas9 patent, despite claims to the contrary from the University of California, Berkeley.
Scientists at UC Berkeley are credited with first developing CRISPR (showing the method could be used to cut DNA in a test tube), and UC Berkeley filed for a patent in May 2012, claiming universal ownership of the technology.
Before a decision was reached on the UC Berkeley application, the Broad Institute applied for a patent showing the method could be used on human cells. This submission came in April 2014, and dealt only with CRISPR as it applies to eukaryotic cells (which make up plants, animals, and humans). The Broad paid to expedite its application, and the patent was granted.
UC Berkeley filed a law suit against the Broad, claiming the Broad’s research was a derivative of UC Berkeley’s work. However judges have now ruled as of February 2017 that the Broad’s research is unique and the patent stands.
If the UC Berkeley patent is granted, the effect will be that those who wish to apply CRISPR to eukaryotic cells will have to pay both the Broad and UC Berkeley for its use.
UC Berkeley has said that it is considering whether to appeal the decision. This leaves members of the biotechnology sector wondering who they will have to pay to use CRISPR as part of a business, and scientists hoping the outcome won’t keep them from continuing their research. However both UC Berkeley and the Broad have indicated their commitment to licensing cheaply to other non-profit institutions.
Regardless of this win for the Broad, the debate will continue as to whether such revolutionary technology should be patented in the first place. But developing medical treatments is an immensely expensive process and having a patent in place can attract investment that might otherwise not happen.
The patent battle had temporarily slowed scientific research making use of CRISPR. However with further advancements in gene editing taking place it may well turn out that CRISPR is not the only game in town, and this law suit is merely a distraction as scientific innovation inevitably finds a way forward.