Allele Specific CRISPR Editing

Sharon Begley, 02 February 2018, STAT, https://www.statnews.com/2018/02/02/crispr-blindness-retinitis-pigmentosa/

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 (https://www.biorxiv.org/content/early/2018/01/29/197962).

Solving the CRISPR Delivery Problem

Megan Molteni, Wired, 26 January 2018, https://www.wired.com/story/what-good-is-crispr-if-it-cant-get-where-it-needs-to-go/

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, https://www.the-scientist.com/?articles.view/articleNo/51500/title/Stem-Cells-Made-by-Modifying-the-Epigenome-with-CRISPR/

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 (https://www.ncbi.nlm.nih.gov/pubmed/29358044).

First Human Trials Using CRISPR in the US

Emily Mullin, MIT Technology Review, 17 Jan 2018, https://www.technologyreview.com/s/609999/us-doctors-plan-to-treat-cancer-patients-using-crispr/

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, https://www.nature.com/articles/d41586-018-00335-8

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 https://www.theatlantic.com/science/archive/2017/12/turning-piglets-into-personalized-avatars-for-sick-kids/548204/

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, https://www.genengnews.com/gen-news-highlights/genetic-differences-could-impact-efficacy-and-safety-of-crispr-therapeutics/81255262

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, https://www.statnews.com/2017/12/08/crispr-analogies-ranked/

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.

CRISPR Converts Microbes to Tape Recorders

GEN News Highlights, 27 Nov 2017, https://www.genengnews.com/gen-news-highlights/crisprcas-used-to-create-microscopic-data-recorder/81255201

Scientists have created a CRISPR/Cas system in E. coli that allows for the recording of events and the time at which they occurred.  This was done by having the cell insert CRISPR spacers at regular occurring sets of time, however when a signal was detected the bacteria would insert a signal sequence instead.  This locus can then be read using pre-existing sequencing tools providing a readout of events.  The researchers hope this technology could be used to record biological events.

Increasing the Potency of T Cell Cancer Therapy

GEN News Highlights, 21 November 2017, https://www.genengnews.com/gen-news-highlights/crispr-editing-creates-tcr-swap-shop-for-cancer-immunotherapy/81255191

In the United Kingdom, Cardiff University researchers have used CRISPR to create T cells up to a thousand times more sensitive to cancer cells.  These cells have been edited to remove their own T-cell receptors, leaving only those targeting cancer cells.  The hope is that custom immunotherapies such as this may one day replace conventional cancer therapies.