Genetic Engineering Publications - GEG Tech top picks

The recent approval of a CRISPR-Cas9 therapy for sickle-cell anemia demonstrates that gene-editing tools can do an excellent job of eliminating genes to cure inherited diseases. But it is still not possible to insert entire genes into the human genome to replace them with defective or deleterious genes. A new technique, called RNA-mediated Precise Transgene Insertion, or PRINT, exploits the ability of certain retrotransposons to efficiently insert whole genes into the genome without affecting other genome functions. PRINT would complement the recognized ability of CRISPR-Cas technology to deactivate genes, perform point mutations and insert short segments of DNA. For PRINT, one piece of delivered RNA encodes a common retroelement protein called the R2 protein, which has several active parts, including a nickase and a reverse transcriptase. The other RNA is the template for the transgenic DNA to be inserted, as well as the elements controlling gene expression

In this study, the authors developed a visualized fluorescent reporter system to detect the specificity and cleavage activity of gRNA. Two gRNAs were designed to target porcine immunoglobulin M and nephrosis 1 genes. The cleavage activity was measured by using the traditional homology-directed repair (HDR)-based fluorescent reporter and the single-strand annealing (SSA)-based fluorescent reporter they established in this study. Compared with the HDR assay, the SSA-based fluorescent reporter approach was a more efficient and dependable strategy for testing the cleavage activity of Cas9/gRNA, thereby providing a universal and efficient approach for the application of CRISPR/Cas9 in generating gene-modified cells and organisms.

The emergence of antibiotic-resistant pathogens represents a major global challenge. In numerous disease areas, current medical practice relies on increasingly aggressive therapies, which can sometimes result in patients experiencing life-threatening infections, including those caused by antibiotic-resistant bacteria. SNIPR001's mechanism of action, as a CRISPR-armed phage therapeutic that specifically targets and eradicates E. coli in the gut, is designed to prevent infections from spreading into the bloodstream and represents a promising advancement against antibiotic-resistant pathogens. This publication represents a significant validation of the ground-breaking technology research done at the laboratories and collaborators of SNIPR Biome, the company pioneering CRISPR-based microbial gene therapy, and also opens up the possibility of targeting other pathogens.  SNIPR001 has been granted a Fast-Track designation by the US Food and Drug Administration, was supported by CARB-X, and SNIPR is currently conducting a Phase 1 trial in the US to evaluate its safety and efficacy in reducing E. coli in the gut without disturbing the overall gut microbiome.