Ranger Biotechnologies has acquired all assets including the Blockmir Technology platform from former Mirrx Therapeutics. The technology uses short highly modified oligonucleotides – Blockmirs – to block specific miRNA binding sites on individual mRNAs. This achieves gene specific upregulation on protein level and sets Ranger’s Technology apart from most other therapeutic modalities which aim to antagonize mRNA or protein activity. Blockmirs are agonists of gene expression and lead to physiologic upregulation of protein levels.
Ranger Biotechnologies has a broad and dominant portfolio of issued patents. The patent estate covers the target mRNAs of more than 300 miRNAs – which means several thousands of different target mRNAs that can be upregulated individually. A composition of matter for a general Blockmir design with improved selectivity and potency is also granted.
Upregulation of therapeutically relevant proteins is applicable in a wide range of diseases spanning from cancer to rare genetic and metabolic disorders where even a small upregulation of a single protein can mean a world of difference for the patients. Blockmirs, sometimes called target protectors or protectomirs, have been used in more than 160 academic research programs worldwide, showing upregulation of many therapeutically relevant targets and underscoring the wide application of this technology.
Together with the Centenary Institute, Ranger Biotechnologies has developed a highly specific Blockmir, CD5-2, which targets VE-Cadherin in blood vessel endothelia. Data from diabetic retinopathy, Cerebral Cavernous Malformations, cancer and ischemia show that control of vascular permeability using CD5-2 is pivotal to prevent disease development and progression and recovery after ischemia. The data further indicates that upregulation of VE-Cadherin using CD5-2 also holds promise for treatment of inflammation and neurodegenerative disease such as Alzheimer’s disease, through modulation of immune cell transmigration.
The data is published individually for each indication investigated:
Targeting vascular endothelial-cadherin in tumor-associated blood vessels promotes T cell-mediated immunotherapy
Yang Zhao, Kaka Ting, Jia Li, Victoria C Cogger, Jinbiao Chen, Anna Johansson-Percival, Shin Foong Ngiow, Jeff Holst, Georges E. R. Grau, Shom Goel, Thorleif Moller, Elisabetta Dejana, Geoffrey W McCaughan, Mark J. Smyth, Ruth Ganss, Mathew A Vadas and Jennifer R Gamble
Cancer Research DOI: 10.1158/0008-5472.CAN-16-3129
Regulation of vascular leak and recovery from ischemic injury by general and VE-cadherin–restricted miRNA antagonists of miR-27
Jennifer A. Young, Ka Ka Ting, Jia Li, Thorleif Moller, Louise Dunn, Ying Lu, Angelina J. Lay, Joshua Moses, Leonel Prado-Lourenço, Levon M. Khachigian, Martin Ng, Philip A. Gregory, Gregory J. Goodall, Anna Tsykin, Ilana Lichtenstein, Christopher N. Hahn, Nham Tran, Nicholas Shackel, James G. Kench, Geoffrey McCaughan, Mathew A. Vadas and Jennifer R. Gamble
Blood 2013 122:2911-2919; doi: https://doi.org/10.1182/blood-2012-12-473017
Therapeutic regulation of VE-cadherin with a novel oligonucleotide drug for diabetic eye complications using retinopathy mouse models
Ka Ka Ting, Yang Zhao, Weiyong Shen, Paul Coleman, Michelle Yam, Tailoi Chan-Ling, Jia Li, Thorleif Moller, Mark Gillies, Mathew A. Vadas, Jennifer R. Gamble
Diabetologia. 2018 Nov 15. doi: 10.1007/s00125-018-4770-4.