Proximal Targeting With dCas Alters Chromatin Structure Allowing Genome Editing

Chen, Fuqiang, et. a. (2017) Nature Communications. 8:14958. https://www.nature.com/articles/ncomms14958

Many different Cas variants have been discovered, each with slightly different activities.  Francisella novicida Cas9 (FnCas9) is one such Cas variant. It is frequently inhibited at genomic loci, presumably due to chromatin formation.  By using dead SpCas9 to target proximally, FnCas9 could cleave at the target site, presumably due to chromatin rearrangements.

CRISPR Corrects Tomato Breeding Mistake

Heidi Ledford, Nature News 18 May 2017, https://www.nature.com/news/fixing-the-tomato-crispr-edits-correct-plant-breeding-snafu-1.22018

Tomatoes have been bred for their large fruit over thousands of years.  To prevent the tomato from dropping mature fruit, breeders in the 1950s crossed the modern tomato with a wild variety discovered in the Galapagos that lacked the weak region of the stem responsible for fruit dropping.  While this trait functioned in the new cross, it also resulted in extra branches that produced flowers, draining the plants resources.  By sequencing many tomato varieties, scientists have now identified the genes responsible for both traits and are using CRISPR to modify the tomato for better yields and fruit retention.

Could CRISPR Save US Citrus Farms?

Heidi Ledford, Nature News, 16 May 2017, https://www.nature.com/news/geneticists-enlist-engineered-virus-and-crispr-to-battle-citrus-disease-1.21997

American Citrus farmers are facing two threats to their crops, the citrus tristeza virus and citrus greening.  Citrus greening is the result of a bacterial infection that causes bitter, misshapen fruits with green lower halves.  To stop the spread of citrus greening, scientists are attempting to use CRISPR/Cas to modify the citrus trees for increased resistance.  Local growers have even helped fund a project to sequence the citrus trees to help identify potential targets.

Beacon Genomics to Commercialize Genome-Wide CRISPR Off-Target Screens

Monica Heger, GenomeWeb, 12 May 2017, https://www.genomeweb.com/sequencing/beacon-genomics-aims-commercialize-technologies-gene-editing-safety

CRISPR off-target effects is of significant concern during the transition of the system from a basic research tool to clinical settings.  The startup Beacon Genomics aims to aid in this process by offering NGS based, off-target screens: GUIDE-seq and CIRCLE-seq.  These non-biased methods rapidly screen the entire genome for potential off-target effects, enabling researchers and clinicians to optimize CRISPR/Cas treatment conditions.

Biology Needs a National Strategy

Amy Webb, Wired, 11 May 2017, https://www.wired.com/2017/05/crispr-makes-clear-us-needs-biology-strategy-fast/

With the fast pace of CRISPR technology, the regulations and laws governing biology research cannot keep up.  This has become apparent with CRISPR genome editing. Despite the potential applications in research, medicine, and agriculture, control over how CRISPR technology is applied is determined by patent control.  In this opinion piece Amy Webb proposes that the United States needs a non-partisan panel of scientists, technologies, ethicists, policy experts, and futurists to develop strategic plans for biology.

Could Casposons Have Given Rise to CRISPR?

Krupovic, M. et. al. (2017) Current Opinion in Microbiology 38:36-43. https://www.ncbi.nlm.nih.gov/pubmed/28472712

Casposons are a superfamily of self-synthesizing transposons found in prokaryotes.  One identified casposon is homologous to the Cas1 endonuclease and could have evolved into the adaption module of the CRISPR/Cas system and the CRISPR repeats.  This opinion publication covers how the casposon system is similar and different from that of CRISPR/Cas and the evidence supporting its evolution into the CRISPR system.

Induced Pluripotent Stem Cells Used to Study Chlamydia Pathogenesis

Yeung, A.T.Y., et. al. (2017) Nature Communications 8:15013. https://www.ncbi.nlm.nih.gov/pubmed/28440293

Chlamydia is a leading sexually transmitted disease and cause of preventable blindness. Cell based systems to study the interactions between Chlamydia and human macrophages remain limited.  Yeung et al. have developed human induced pluripotent stem cell-derived macrophages that are readily modifiable using CRISPR/Cas9 to study the interactions between Chlamydia and human macrophages.

New CRISPR Clinical Trial

GenomeWeb 28 April 2017 https://www.genomeweb.com/scan/another-crispr-trial-begins

Chinese researchers are starting a clinical trial investigating use of CRISPR/Cas9 in cancer therapy.  Patients with aggressive gastric cancer, nasopharyngeal carcinoma, and lymphoma will have their own modified immune cells reinjected in the hope that they will target and destroy cancer cells.

CRISPR Pill Could Replace Antibiotics

Emily Mullin, MIT Technology Review, 17 April 2017, https://www.technologyreview.com/s/604126/edible-crispr-could-replace-antibiotics/

Traditional antibiotics not only target human pathogens, but eliminate much of the gut microbiome.  Delivery of a bacteriophage containing a customized CRISPR message to the site of infection could target only specific pathogenic bacteria, thus reducing or even eliminating negative effects on beneficial bacteria.  These types of tools may someday replace our current antibiotics, though there is still years of research ahead before this reaches consumers.

Human ALS iPSCs Corrected Through CRISPR/Cas9 Treatment

Wang, L. et. al. (2017) Protein Cell. https://www.ncbi.nlm.nih.gov/pubmed/28401346

ALS is a neurodegenerative disease, with mutations in SOD1 and FUS associated with familial ALS.  Using CRISPR/Cas9 Wang et al. corrected human iPSCs generated from fibroblasts of familial ALS patients containing SOD1 and FUS mutations.  These regenerated cells were used for transcriptome comparison studies to the mutated cells with close to 900 aberrant transcripts identified.  Use of this system could lead to potential therapies for ALS patients with SOD1 and FUS mutations.