Feng Zhang’s SEND mRNA delivery platform; plus in vivo CRISPR screening with MIC-Drop and more

Researchers in the lab of CRISPR pioneer Feng Zhang unveiled an mRNA delivery platform based on endogenous human proteins with potential to get around one of the biggest issues with viral vectors: immunogenicity. Described in Science, the platform — dubbed SEND — combines the mammalian retrovirus-like protein PEG10, which is derived from human cells, with the cargo mRNA and a fusogenic protein that enables cell entry. Also going for the system is that PEG10 is more highly expressed in the human developing thymus, the site of T cell tolerance induction, than other capsid-forming gag homologs, further upping its chances of avoiding immunogenicity. The Broad Institute team showed SEND-mediated delivery of sgRNA and Streptococcus pyogenes Cas9 cargo was functional in mouse and human cell lines, generating 30% and 40% indels, respectively.

Technology developed at the University of Utah could enable large-scale CRISPR screening in vertebrates, according to a paper published in Science. Called MIC-Drop, the platform utilizes droplet microfluidics, single-needle Cas9-gRNA ribonucleoprotein injections and DNA barcoding to facilitate rapid screening of hundreds to thousands of genes. In a validation experiment in zebrafish, scientists screened 188 poorly characterized genes enriched in embryonic heart tissue relative to skeletal muscle, and identified 13 genes whose loss led to abnormal cardiac development, arrhythmia and other phenotypes. The team said MIC-Drop marks the first time screens using CRISPR have been possible in animal models...