Intravenous delivery of an adenine base editor and a single-guide RNA for the Fah gene can correct an A>G splice-site mutation in an adult mouse model of tyrosinaemia.
The ever-improving knowledge of the organization and composition of the genome and the epigenome, together with the expanding technological toolbox for the manipulation of DNA with increasing precision, are propelling the exploration of how genome-engineering approaches can be translated to tackle diseases that escape conventional therapies. [Editorial]
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Genome-edited human pluripotent stem cells and genome-edited mouse models reveal that combinatorial genetic interactions contribute to the complex genetic heritability of human cardiomyopathy.
CRISPR–Cas9-mediated genome editing can be activated locally in vivo via an applied magnetic field, after complexation of magnetic nanoparticles with recombinant baculoviral vectors packaging the CRISPR–Cas9 machinery.
Genome-edited skin epidermal stem cells protect mice from cocaine-seeking behaviour and cocaine overdose
The transplantation of skin cells genetically modified to express an enzyme that hydrolyses cocaine into mice leads to long-lasting levels of the enzyme in the circulation and protects the mice from cocaine-seeking behaviour and cocaine overdose.
Nanoparticle delivery of CRISPR into the brain rescues a mouse model of fragile X syndrome from exaggerated repetitive behaviours
Gene editing of a single gene in the brain of an adult mouse model of fragile X syndrome, achieved via the intracranial injection of a nonviral Cas9 delivery vehicle, rescues mice from the exaggerated repetitive behaviours caused by the disease.
A cloud-based machine-learning software that scores individual guide–target pairs and provides an overall summary score for a given guide that outperforms competing algorithms for the prediction of CRISPR–Cas9 off-target effects.
A model accounting for the properties of the local chromatin environment predicts the modulation of patterns in gene expression and helps screen for chemotherapeutic adjuvants that lead to an enhanced therapeutic response in cancer cells.
Ectopic expression of RAD52 and dn53BP1 improves homology-directed repair during CRISPR–Cas9 genome editing
The expression of two specific DNA-repair factors promotes homology-directed repair and enhances the precision of CRISPR–Cas9 gene editing at multiple loci in human cells, including patient-derived induced pluripotent stem cells.
Nanoparticle delivery of Cas9 ribonucleoprotein and donor DNA in vivo induces homology-directed DNA repair
Gold nanoparticles carrying Cas9 ribonucleoprotein and donor DNA, and complexed with endosomal disruptive polymers, correct the DNA mutation that causes Duchenne muscular dystrophy in mice, with minimal off-target effects.
An array of chemically engineered CRISPR RNAs and AsCpf1 messenger RNAs leads to improvements in gene-cutting efficiency up to about 300% with respect to unmodified CRISPR RNA and plasmid-encoding AsCpf1.
News & Comment
The simplicity and powerful capabilities of CRISPR have led to an explosion of genome-editing applications. Their continued development should be nurtured by scientific and legal environments that discourage and penalize irresponsible uses of the technology.
Graftable skin expressing an enzyme that metabolizes cocaine may offer a new strategy to treat cocaine addiction.
Magnetic nanoparticles complexed with recombinant baculoviral vectors containing the CRISPR–Cas9 machinery enable the local magnetic activation of genome editing.
Human cardiomyocytes and mice edited to harbour gene variants found in patients with dilated cardiomyopathy reveal combinatorial genetic interactions that contribute to the complex genetic heritability of the disease.
Widespread editing of the mutated DMD gene by CRISPR–Cas9, systemically delivered via an adeno-associated virus, restores dystrophin expression in a canine model of Duchenne muscular dystrophy.
The optimization and diversification of methods for manipulating the genome will enable new therapeutic solutions.
A theoretical model of chromatin packing heterogeneity predicts patterns in gene expression and can be used to screen for effective chemotherapeutic adjuvants.
The expression of two DNA repair factors improves the recombination of single-stranded oligodeoxynucleotides with Cas9-induced double-strand breaks, facilitating precise and efficient gene editing.
The DNA mutation that causes Duchenne muscular dystrophy in mice can be corrected, with minimal off-target effects, by gold nanoparticles carrying the CRISPR components.