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

CRISPR therapies are increasingly being developed. However, a recent study has identified a new danger associated with CRISPR-Cas9-based therapies. The double-stranded DNA breaks introduced during CRISPR editing could lead to chromothripsis, an extremely damaging form of genomic rearrangement that results in the breakup of individual chromosomes and the subsequent reassembly of the pieces in a disordered order. Although most cells do not remain viable after undergoing such radical modification, those that do can, in theory, express oncogenic fusion proteins or result in the deregulated expression of particular genes that can cause problems. Other studies have reported CRISPR-Cas9-induced DNA deletions and large-scale chromosomal rearrangements, CRISPR-Cas9 activation of the tumour suppressor protein p53, which could select for inactivating and cancer-causing mutations, and the induction of large chromosomal truncations. In addition, the presence of pre-existing antibodies and T cells directed against Cas9 enzymes in large percentages of the population could compromise efficacy. However, base and primer editing methods, which use single strand nicks rather than double strand breaks to introduce a modification, are much less likely to cause chromothripsis.