Researchers Unable to Reproduce CRISPR Off-Target Problems

Kristen V Brown, Gizmodo, 05 March 2018, https://gizmodo.com/after-a-few-hiccups-all-bets-are-on-crispr-again-1823521006

In 2017, a publication raised the alarm over potential off-target effects during CRISPR therapies.  Multiple research groups set out to reproduce the study and found that the off-target effects initially reported were over-stated.  These new studies have worked to restore confidence that the CRISPR gene editing technology may be suitable for gene therapies.

CRISPR Knock Out of FREP1 Suppresses Malaria Infection in Mosquitoes

EurekaAlert! 8 March 2018, https://www.eurekalert.org/pub_releases/2018-03/p-cts030218.php

A new study in PLOS Pathogens demonstrates that CRISPR knockout of FREP1 in Anopheles gambiae mosquitos suppressed Plasmodium parasites infections.  This could potentially be used as a gene drive mechanism to eliminate malaria infections.  The inactivation of FREP1 did result in reduced blood-feeding, lower egg hatching rate, slowed development, and reduced longevity after feeding on blood, raising concerns that the modified mosquito may not be able to compete with its wild-type counterparts.

Modeling CRISPR Hybridization Kinetics

Klein, M. et. al. (2018) Cell Reports 22:1413-1426. https://www.ncbi.nlm.nih.gov/pubmed/29425498

For CRISPR-based therapies to become viable, the off-target effects of the nucleases must be controlled.  To enhance the guide selection, this paper presents a kinetic model using four parameters that can mechanistically explain guide binding and off-target predictions.

Pig Organs Could Provide Relief to Those in Organ Failure

Alice Park, Time Magazine, 15 February 2018, http://time.com/5159889/why-pig-organs-could-be-the-future-of-transplants/

Due to limited amounts of viable donated organs, thousands of people die each year in the US waiting for a transplant.  Scientists have long desired to find a viable replacement for donated human organs and may have one in CRISPR modified pig organs.  Pig organs are roughly the same size and shape as human organs, however the presence of viruses in the pig genome have proven a significant barrier to use in clinical settings.  Now a company founded by George Church has used CRISPR to inactivate these viruses and generated 15 pigs that could be viable stocks for kidney, liver, lungs, or pancreas transplants.

Cellectis Granted CRISPR/Cas Patents for T-Cell Modification

Business Wire, 13 February 2018, https://www.businesswire.com/news/home/20180212006461/en/Issued-U.S.-Patents-Granted-Cellectis-CRISPR-T-Cells

Cellectis has been granted patents for a T-cell genetic engineering method using transient expression of the CRISPR/Cas9 components.  A similar patent has already been issued by the European Patent Office.  This technology will be used to develop engineered CAR T-cells and the technology will be available for licensing.

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).

Increasing Homology Directed Repair Efficiency by “Cold Shock”

Guo, Q., et. al. (2018) Scientific Reports. 8:2080. https://www.ncbi.nlm.nih.gov/pubmed/29391533

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, 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).

European Patent Office Revokes Broad Institutes Patent

Kelly Servick, Science, 18 Jan 2018, http://www.sciencemag.org/news/2018/01/broad-institute-takes-hit-european-crispr-patent-struggle

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.