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Science Paper on Spatial-Controlled Genome Editing

A CRISPR-Cas13a-based system for spatial-controlled genome editing and cancer therapy is reported in Science Advances this week. CRISPR-Cas13a has emerged as a powerful system for RNA silencing, capable of cleaving both targeted RNA and nearby non-targeted RNA. This so-called collateral effect suggests that it may be effective in cancer treatment, enabling resistance to tumors' escape mechanisms, but the excessive and constantly active Cas13a also raises safety concerns. Thus, using CRISPR/Cas13a therapeutically requires controlling the RNase activity of Cas13a across spatial dimensions. To that end, Chongqing Medical University scientists developed hierarchical self-uncloaking CRISPR-Cas13a–customized RNA nanococoons — dubbed RNCOs-D — which feature tumor-specific recognition and spatial-controlled activation of Cas13a. RNCOs-D consists of programmable RNA nanosponges capable of targeted delivery and caging of chemotherapeutic drugs, along with nanocapsules anchored on the nanosponges for cloaking Cas13a/CRISPR RNA ribonucleoprotein activity. The tumor intracellular acidic microenvironment induces self-uncloaking of nanocapsules to allow spatial-controlled gene silencing by the intact CRISPR-Cas13a system and drug release via Cas13a transcleavage after cis-recognition of the mRNA target. The researchers demonstrate their approach by silencing mRNA for the tumor-specific mutation EGFR variant III in glioblastoma cells in vitro and in vivo.

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The Scan

Pig Organ Transplants Considered

The Wall Street Journal reports that the US Food and Drug Administration may soon allow clinical trials that involve transplanting pig organs into humans.

'Poo-Bank' Proposal

Harvard Medical School researchers suggest people should bank stool samples when they are young to transplant when they later develop age-related diseases.

Spurred to Develop Again

New Scientist reports that researchers may have uncovered why about 60 percent of in vitro fertilization embryos stop developing.

Science Papers Examine Breast Milk Cell Populations, Cerebral Cortex Cellular Diversity, Micronesia Population History

In Science this week: unique cell populations found within breast milk, 100 transcriptionally distinct cell populations uncovered in the cerebral cortex, and more.