Gold Nanoparticles Deliver CRISPR in Muscular Dystrophy Treatment

Sophia Ktori, GEN News Highlights, 04 October 2017, http://www.genengnews.com/gen-news-highlights/crispr-nanoparticles-repair-duchenne-muscular-dystrophy-gene/81255009

Scientists working on CRISPR delivery have developed a gold nanoparticle that encapsulates the CRISPR/Cas machinery for delivery to cells.  This new technique, coined CRISPR-Gold, was published in Nature Biomedical Engineering (https://www.nature.com/articles/s41551-017-0137-2).  In the paper the authors demonstrated CRISPR-Gold’s ability to correct the mutated dystrophin gene in a mouse model, with mice receiving CRISPR-Gold treatment displaying two-fold improvement in hanging time in a four-limb hanging test, compared to control mice.

CRISPR Delivery in the Ear

Antonio Regalado, MIT Technology Review, 22 September 2017, https://www.technologyreview.com/s/608899/the-easiest-place-to-use-crispr-might-be-in-your-ear/

One of the major challenges with CRISPR based medical therapies is delivering the necessary components.  One group at the Massachusetts Eye and Ear Infirmary are working on delivering the CRISPR/Cas machinery into mice ears to cure a genetic defect that results in gradual hearing loss.  In the best cases the mice retained significant hearing at two months of age.

Chinese Research Team Fix Genetic Disorder in Human Embryos

David Cyranoski, 02 October 2017, Nature News, http://www.nature.com/news/chinese-scientists-fix-genetic-disorder-in-cloned-human-embryos-1.22694

A new report in Protein and Cell (https://www.ncbi.nlm.nih.gov/pubmed/28942539) is the latest in a string of human embryo CRISPR publications.  Using a modified CRISPR/Cas9 system tethered to a second enzyme that can swap individual DNA bases, the researchers targeted an A to G point mutation that results in β-thalassemia.  Eight of the 20 cloned embryos contained a corrected copy of the gene, possibly curing the recessive disorder.  The scientists were careful to point out that not all cells in the embryo were modified, which could have unintended consequences.

New Cas9 Mutations Increase Accuracy

Chen et. al. (2017) Nature. https://www.ncbi.nlm.nih.gov/pubmed/28931002

Researchers using FRET to study previously engineered high-fidelity Cas9 (SpCas9-HF1) and enhanced Cas9 (eSpCas9), identified that these versions are trapped in an inactive state when bound to off-target sites.  Using this observation and rational protein engineering, the researchers made additional modifications to the REC3 domain to prevent activation of the HNH nuclease domain unless the guide RNA and target DNA match is very close.  This new Cas9, coined Hyper Cas9 (HypaCas9) maintains the native Cas9 on target efficiency, but decreases the number of off-target events.

Getting CRISPR into the Body

Emily Mullin, MIT Technology Review, 22 September 2017, https://www.technologyreview.com/s/608898/five-ways-to-get-crispr-into-the-body/

While CRISPR has shown great promise in the lab, its clinical application is more difficult due to delivery challenges.  Researchers are diligently working on this problem, with this article covering five possible ways to deliver the CRISPR/Cas machinery including gels/creams, edible CRISPR, ear injections, skin grafts, and ex vivo therapy.

CRISPR Used to Understand Human Embryos’ Days

Heidi Ledford, Nature News, 20 September 2017, http://www.nature.com/news/crispr-used-to-peer-into-human-embryos-first-days-1.22646

Developmental biologists in the United Kingdom have identified differences in the OCT4 gene between mouse and human embryos by using CRISPR/Cas9 to disrupt OCT4.  While disruption of OCT4 results in abnormal embryo development in both mice and human embryos, human embryos lacking the protein quit developing earlier than mouse embryos and showed a completely different pattern of gene expression.  Additionally, the OCT4 human embryo mutant showed abnormalities in cells that give rise to the placenta.  The researchers hope their work can be sued to improve IVF treatments and explain why some pregnancies fail.

CRISPR Allows for Target Mapping in Rare Cancers

Sharifnia, T., et. al. (2017) Cell Chemical Biology. 24:1075-1091. https://www.ncbi.nlm.nih.gov/pubmed/28938087

Rare cancers have traditionally been difficult to study due to low incidence and limited sample availability.  However, new technologies, such as sequencing, have allowed for a greater understanding of the underlying genetic causes.  In tandem with sequencing technologies, CRISPR/Cas and small molecule screens have allowed researchers to rapidly screen rare cancers for possible mechanisms and treatments.

It’s Time for Your Nobel Prize Predictions

Sharon Begley, STAT, 25 September 2017, https://www.statnews.com/2017/09/25/nobel-prize-predictions/

The season of Nobel Prize awards has arrived, and with it comes a slew of predictions.  This year, STAT has identified who they believe has the best chance of winning the Nobel Prize in Medicine; including the CRISPR crowd of Emmanuelle Charpentier, George Church, Jennifer Doudna, and Feng Zhang.  The only problem being each Nobel Prize can only be awarded to three people.

CRISPR Reveals How Butterflies Get Their Color

Rachael Lallensack, Nature News, 18 September 2017, http://www.nature.com/news/crispr-reveals-genetic-master-switches-behind-butterfly-wing-patterns-1.22628

Two new studies in the Proceedings of the National Academy of Sciences (http://www.pnas.org/content/early/2017/08/29/1709058114, http://www.pnas.org/content/early/2017/08/29/1708149114) provide insight into butterfly wing color.  The studies identified two genes, WntA is responsible for creation of the coloring pattern and borders, while optix fills the color within the borders.  Understanding butterfly coloration could provide insights into adaptations such as mimicry.

Reversing CRISPR Gene Drives

Vella, M.R. et. al. (2017) Scientific Reports 7:11038. https://www.ncbi.nlm.nih.gov/pubmed/28887462

CRISPR/Cas gene drives could be used to eliminate vector-borne diseases such as malaria and Lyme disease. However, release of modified organisms is controversial in part due to unforeseen consequences.  Developing strategies for gene drive reversal could prove useful if such problems arise.  This paper develops models to evaluate the effectiveness of gene drive counter-measures in order to evaluate their potential use.