Allele Specific CRISPR Editing

Sharon Begley, 02 February 2018, STAT,

Many diseases are the result of a single mutated allele.  To correct these with a CRISPR-based system, the mutated allele should be targeted while the healthy allele is left untouched.  In one of the first papers to be published in The CRISPR Journal, researchers have developed a method to target the “broken” allele while leaving the healthy allele untouched.  This proof of concept work was done in a mouse retinitis pigmentosa model, where blindness is caused by a single nucleotide change in one allele.  Results have been published on the BioRxiv prepress server (

Increasing Homology Directed Repair Efficiency by “Cold Shock”

Guo, Q., et. al. (2018) Scientific Reports. 8:2080.

Homology directed repair (HDR) has long been plagued by low efficiency, limiting its use in gene editing.  Researchers working with induced pluripotent stem cells (iPSC) have found that by incubating cells at 32°C for 24-48 hours post-transfection, HDR efficiency can be increased by two- to ten-fold.  This type of research could allow for more efficient use of CRISPR HDR.

Solving the CRISPR Delivery Problem

Megan Molteni, Wired, 26 January 2018,

Many different research groups and companies are working on the creation of CRISPR-based gene therapies. However, delivery of these therapies remains a significant obstacle.  Traditionally, gene therapies have been packaged in Adeno-associated viruses, but the size of the CRISPR machinery prevents this method of delivery.  To solve these problems, researchers are working on novel delivery mechanisms, including the use of gold nanoparticles.  Notably, a UC-Berkeley spin-off company has been created to focus solely on delivery of the CRISPR/Cas machinery.

Epigenome Modifications Create IPSCs

Abby Olena, The Scientist, 25 January 2018,

Transitioning somatic cells into induced pluripotent stem cells (IPSCs) has traditionally been a laborious process.  By coupling dCas9 with epigenetic remodeling, researchers were able to activate either Sox2 or Oct4, converting the transfected cells into IPSCs.  The results of this study were published in Cell Stem Cell (

European Patent Office Revokes Broad Institutes Patent

Kelly Servick, Science, 18 Jan 2018,

While the Broad Institute has been considered the winning party in the US CRISPR patent battle, the European landscape is a different story.  Due to technical errors over listed inventors and claimed priority dates, the European patents filed by the Broad Institute have been revoked.  While the Broad Institute is expected to appeal the decision, the likelihood of success is slim.

First Human Trials Using CRISPR in the US

Emily Mullin, MIT Technology Review, 17 Jan 2018,

The first human CRISPR trials are set to start anytime at the University of Pennsylvania, where doctors will modify human immune cells to target cancer.  The first study will have a maximum of 18 patients with multiple myeloma, sarcoma, or melanoma.  This type of ex vivo editing followed by injection of the modified cells should prevent the potential immune responses reported on earlier.  Additional trials are scheduled to begin later this year in Europe.

Could the Immune System Prevent CRISPR Therapies?

Heidi Ledford, Nature, 08 Jan 2018,

According to research published on the preprint server BioRxiv, 79% of studied blood samples contained antibodies for Staphylococcus aureus Cas9 and 65% of samples contained antibodies for Streptococcus pyogenes Cas9.  Additionally, 46% of the 13 adult participates contained T cells targeting S. aureus Cas9.  While these data have not been peer-reviewed, it demonstrates potential challenges faced by in vivo editing with Cas9.

Turning Piglets into Personalized Avatars

Ed Yong, The Atlantic, 13 December 2017

Certain diseases have been woefully understudied by the scientific community for a variety of reasons.  Neurofibromatosis type 1 or NF-1, is one such disease that results from mutations in the Neurofibromatosis-1 gene.  Since many different mutations causes the disease, each with their own symptoms, it has been challenging to develop models to study treatment options.  CRISPR could potentially be used to create swine models with the exact mutation of an affected individual allowing for treatments to be screened for their efficacy prior to use in humans.

CRISPR May Not Be a One Size Fits All Therapy

GEN news Highlights, 12 December 2017,

CRISPR has been described as having the potential to revolutionize gene therapy, however innate genetic diversity may hinder mass produced treatments.  Natural variation in DNA sequence among patients indicates that CRISPR therapy may have to be individualized to avoid off-target effects and maximize efficacy.  With the first human CRISPR trials currently ongoing, we may have a better understanding of its therapeutic potential soon.

The Best and Worst of CRISPR Analogies

Rebecca Robbins, STAT, 8 December 2017,

Explaining the CRISPR/Cas system can be challenging, especially to those not actively involved in the science.  To help better explain what CRISPR can and cannot do, STAT has ranked the best and worst analogies used across media sources.