Generation of Gene-Modified Cynomolgus Monkey via Cas9/RNA-Mediated Gene Targeting in One-Cell Embryos

Niu et al. Cell (2014) 156:836-843.

Monkeys are an important model for studying human disease and developing drug therapies.  However their use has been limited by the inability to produce specific genetic modifications.  By using the CRISPR/Cas9 system Niu et al. were able selectively disrupt both PPAR-γ and RAG1 in the cynomolgus monkey (Macaca fascicularis) with no off-target modifications detected, thus demonstrating that CRISPR/Cas9 technology could be used to further expand our knowledge of human disease through the use of monkey models.

In vivo engineering of oncogenic chromosomal rearrangements with the CRISPR/Cas9 system.

Maddalo et al. Nature (2014) 516:423-427.

Many human cancers are the result of chromosomal rearrangements which has made modeling certain cancers in mice challenging.  Using CRISPR/Cas9 gene editing Maddalo et al. were able to induce chromosomal rearrangements similar to those found non-small cell lung cancers in mouse lung tissue.  CRISPR/Cas9 modified mice developed lung tumors when compared to control mice demonstrating the capability of CRISPR/Cas9 technology to selectively edit mouse tissues to study human cancers.

Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype.

Yin et al. Nat Biotechnol (2014) 32:551-553.

Fatal hereditary diseases are potential targets for CRISPR/Cas9 gene therapies using homology directed repair.  Using a mouse model for hereditary tyrosinemia type I – which causes liver damage and ultimately failure due to the buildup of toxic metabolites in the tyrosine catabolic pathway – d containing the same G to A point mutation found in the human form of the disease, Yin et al where able to repair the gene and reverse the associated phenotypes.  While CRISPR/Cas9 gene editing has yet to be used to correct human genetic disease, results such as this provide a promising outlook for treatment of genetic diseases.

An Arcane Patent Law May Decide Crispr’s Big Legal Fight

Sarah Zhang,, January 5th, 2016

The dispute over who owns the CRISPR patents has triggered an outdated patent law known as an interference proceeding to determine the validity of the Broad Institutes patents.  Interference proceedings were removed from patent disputes in 2013, however, since both the Broad Institutes and University of California-Berkely’s patents were filed prior to 2013 the dispute triggered what may be the last such proceeding.  Interference proceedings resemble a court, a panel of three judges listen to oral arguments to determine who invented the technology first.  Berkeley requested the interference proceeding after all the CRISPR patents were awarded to the Broad Institute.  US patent law now uses a first to file and not first to invent criteria to settle disputes.

Cambridge startup Editas plans to test IPO market for biotechs

Robert Weisman.  The Boston Globe. January 5th, 2016

Editas Medicine Inc. has filed for an IPO worth up to $100 million in stock.  Editas was founded in 2013 to develop CRISPR/Cas9 technology licensed from the Broad Institute for medical therapies and raised $120 million in private investments last August.

A proposed regulatory framework for genome-edited crops

Huang S et al. Nature Genetics (2016) 48:109-111.

CRISPR/Cas9 gene editing holds great potential to improve agriculture crops.  However, before CRISPR/Cas9 gene editing can expand the regulatory framework needs clarification.  In this commentary Huang et al. propose regulating crops in a product-based over a technology-based approach.  In this method gene edited crops would be regulated like conventionally bread crops while genetically modified crops (i.e. those that contain transgenes), would continue to be regulated as they are today.

CRISPR/Cas9-mediated somatic correction of a novel coagulator factor IX gene mutation ameliorates hemophilia in mouse.

Guan, Y et. al. EMBO Mol Med (2016)

Hemophilia B is a genetic blood clotting disorder that results from a mutation in coagulator factor IX (FIX) normally treated through intravenous deliver of FIX.  As an increase in FIX levels by as little as 1% can lead to significant clotting improvement, Hemophilia B is uniquely suited for gene therapy treatment.  Guan et al. utilized the CRISPR/Cas9 system and homology-directed repair to correct the mutation in the FIX gene.  While the HDR rate was found to be 0.56% efficient with a single-stranded DNA donor and 1.5% efficient with a double-stranded plasmid donor, the rate of repair was great enough to restore hemostasis.

CRISPR helps heal mice with muscular dystrophy

31Jocelyn Kaiser, Science Magazine, December 31st, 2015.

Duchenne muscular dystrophy (DMD) is a severe form of muscular dystrophy that primarily affects boys and usually results in death around age 25.  DMD is the result of defects or missing DNA in 79 exons that make up the dystrophin gene.  Due to the large size of the dystrophin genes, traditional gene therapy approaches have not been able to fully replace the faulty dystrophin gene.  In the December 2015 edition of Science, three independent groups report using CRISPR/Cas9 technology to remove defective exons of the dystrophin gene in young mice resulting in a truncated form of dystrophin (,,  While the treated mice showed considerable improvement compared to the controls, the treatment cannot be considered a cure since they did not perform as well on muscle tests as normal mice.  Despite its shortcomings, this technique 31could improve the quality of life for those living with DMD.

Bayer in Venture With Gene-Editing Startup

Christopher Alessi and Jonathan Rockoff, The Wall Street Journal, December 20th, 2015.

Germany based Bayer AG has partnered with CRISPR Therapeutics AG to develop gene editing therapies for conditions such as hemophilia, infant heart disease, and Stargardt blindness.  CRISPR Therapeutics was founded by Dr. Emmanuelle Charpentier, co-author of the breakthrough 2012 CRISPR Science paper with Dr. Jennifer Doudna. The deal is worth $300 million over five years with Bayer acquiring a $35 million stake in CRISPR Therapeutics.