Suzuki, K., et. al. Nature (2016) https://www.ncbi.nlm.nih.gov/pubmed/27851729
In vivo integration of a transgene has historically been the main challenge to advancing gene therapy due to its inefficiency, especially in non-dividing cells. Suzuki et. al. developed a CRISPR/Cas9 system using a novel homology-independent targeted integration strategy to knock-in DNA sequences in both dividing and non-dividing cells. In order to demonstrate the techniques therapeutic potential, Suzuki et. al. used this technique to partially restore retinal function in a retinal degeneration rat model.
David Cyranoski, Nature News, 15 November 2016, http://www.nature.com/news/crispr-gene-editing-tested-in-a-person-for-the-first-time-1.20988
A group at Sichuan University has injected CRISPR edited cells into a patient with aggressive lung cancer. The edited cells contain a disabled PD-1 gene which acts to slow down a cell’s immune response. The theory is that the edited cells will be able to seek out and destroy the cancer cells. A total of 10 patients are planned to participate in this clinical trial with each receiving two, three, or four injections with each patient monitored for six months to determine the safety of the treatment.
Andrew Joseph, STAT News, 7 November 2016, https://www.statnews.com/2016/11/07/crispr-patent-case-oral-arguments/
December 6, 2016 will be the first time oral arguments are heard in the CRISPR patent case between the Broad Institute and UC-Berkeley. Each party will have 20 minutes to present their case and 5 minutes to rebut the opposing side. The three presiding judges will then be able to question both parties on the many filled motions. The hearing will be open to the public.
Julie Steenhuysen, Reuters, http://www.reuters.com/article/us-gene-editing-crispr-idUSKBN13300A
Scientists from Stanford University have been able to reverse sickle cell formation using stem cells derived from patients. With this proof of concept in hand, Dr. Matthew Porteus, senior author of the study, plans to approach the FDA with pre-clinical data demonstrating that this method is ready for clinical trials. The plan is to use CRISPR technology to edit stem cells outside of the patient and then reintroduce them. When this procedure was performed in mice enough of modified cells thrived in the bone marrow to potentially cure sickle cell disease.
Jon Cohen, 3 November 2016, Science Magazine, http://www.sciencemag.org/news/2016/11/one-our-reporters-tried-do-crispr-he-failed-miserably
During a recent interview with Science Magazine a researcher stated that “CRISPR may sound intimidating, but it is so simple to use that ‘any idiot’ could do it.” To confirm this, Jon Cohen met with Sanford Burnham Prebys Medical Discovery Institute post-doc Roland Wagner to give it a try. Cohen discovered that while CRISPR gene editing is vastly simpler than previous methodologies, training in molecular biology is still required.
Andrew P. Han, GenomeWeb, 28 October 2016, https://www.genomeweb.com/gene-silencinggene-editing/crispr-patent-interference-likely-heads-oral-arguments-over-preliminary
The final deadline for filing written arguments related to preliminary motions has passed in the CRISPR patent battle. One of the motions filed by the Broad institute claims that their patents do not interfere with those filed by UC-Berkeley. In turn, UC-Berkeley has countered that the Broad Institute’s use of a smaller Cas9 and nuclear localization signal was the next logical step and therefore not patentable. Additionally, UC-Berkeley claims that the use of a single guide RNA is separate from the larger dispute. Together these motions create the potential for both UC-Berkeley and the Broad Institute to walk away with pieces of the CRISPR intellectual property landscape.
Kvon, E. Z., et. al. (2016) Cell 167:633-642 https://www.ncbi.nlm.nih.gov/pubmed/27768887
Researches have now identified a single long range limb enhancer of Sonic hedgehog responsible for normal limb development in vertebrates. By mutating the enhancer, Kvon et. al. were able to prevent normal limb development in mice and create a “Serpentized” mouse that lacks long limbs. This transcription factor is conserved throughout vertebrates including fish but is not found in snakes.
Bahal, R., et. al. (2016) Nature Communications 7:13304.
Beta Thalassemia is a blood disorder caused by mutations in the HBB gene resulting in low levels of hemoglobin. As the genetic cause has been thoroughly characterized, it has been an attractive target for potential gene editing treatments, especially with the CRISPR/Cas9 explosion. However, clinically significant levels of gene editing have been difficult to achieve. Using a triplex-forming peptide nucleic acid coupled with a nanoparticle delivery system, Bahal et. al. were able to achieve a clinically relevant 7% gene editing in mice. This result demonstrates that gene editing techniques other than CRISPR/Cas9 may become clinically relevant.
Sharon Begley, STAT News, 25 October 2016, https://www.statnews.com/2016/10/25/crispr-identifies-hiv-genes/
Scientists have known that mutations in certain genes, such as CCR5, impart resistance to HIV/AIDS, however the number of known HIV related genes has been low due to screening limitations. With CRISPR/Cas9, scientists reduce the time required to screen large number of genes from years to months. A recent publication in Cell Reports used CRISPR/Cas9 to mutate 45 genes, in both individuals and in combinations, to identify additional genes related to HIV infection, ultimately identifying 6 candidates. While it is not yet known if these newly identified genes are suitable for clinical targeting, the ability to perform massive genetic screens could allow for additional HIV/AIDS treatments.
Antonio Regalado, 20 October 2016, MIT Technology Review, https://www.technologyreview.com/s/602633/stop-gene-spills-before-they-happen/
MIT biology professor Kevin Esvelt helped develop the CRISPR/Cas9 gene drive and is coauthor on a gene drive patent application. Esvelt is concerned that gene drive technology developed behind closed doors could lead to a skeptical public slowing the use of the gene drive technology. In an attempt to prevent this, Esvelt has proposed using his patent rights to force scientists into being 100% open about their gene drive work and requiring safety procedures to prevent escape. Since patent law states that the holder can stop anyone from making or using the technology, Esvelt may have the legal right to force full disclosure and safety compliance.