GeneRide™

GeneRide™

LogicBio is a breakthrough gene therapy company founded on two core platform technologies.

The first is GeneRide™, a promoterless, nuclease-free genome editing technology that addresses key shortcomings of current in vivo gene therapy approaches. GeneRide™ achieves high expression of therapeutic proteins by harnessing homologous recombination to integrate transgenes site-specifically into the genome. This provides a durable cure from a one-time treatment.

In addition to GeneRide™, LogicBio also has access to a library of synthetic, non-pathogenic, recombinant adeno-associated viral (rAAV) vectors developed at Stanford University that provide better predictability of vector performance in clinical trials.

Our liver-directed GeneRide™ vectors encode a therapeutic transgene preceded by a 2A-peptide coding sequence, flanked by homology arms spanning the Albumin gene (Alb) stop codon. Integration of the transgene at the Alb locus is facilitated by the natural process of homologous recombination, without the use of exogenous nucleases.

Following integration, expression of the transgene is driven by the endogenous Alb promoter. The transgene is fused to Alb at the DNA and RNA levels, but translated as two separate proteins as the result of ribosomal skipping facilitated by the 2A peptide.

Publications

Lisowski L et al. Selection and evaluation of clinically relevant AAV variants in a xenograft liver model. Nature. 2014 Feb 20;506(7488):382-6. doi: 10.1038/nature12875. Epub 2013 Dec 25.

Barzel A, et al. Promoterless gene targeting without nucleases ameliorates haemophilia B in mice. Nature. 2015 Jan 15;517(7534):360-4. doi: 10.1038/nature13864. Epub 2014 Oct 29.

Nygaard S, et al. A universal system to select gene-modified hepatocytes in vivo. Sci Transl Med. 2016 Jun 8;8(342):342ra79. doi: 10.1126/scitranslmed.aad8166.

Porro F, et al. Promoterless gene targeting without nucleases rescues lethality of a Crigler-Najjar syndrome mouse model. EMBO Mol Med. 2017 Oct;9(10):1346-1355. doi: 10.15252/emmm.201707601.

Borel F, et al. Survival Advantage of Both Human Hepatocyte Xenografts and Genome-Edited Hepatocytes for Treatment of α-1 Antitrypsin Deficiency. Mol Ther. 2017 Nov 1;25(11):2477-2489. doi: 10.1016/j.ymthe.2017.09.020. Epub 2017 Sep 25.