miRNA therapeutics targeting RAS networks

High anti-tumor activity for wide range of RAS mutated cancers by chemically-modified miR-143#12 (Tumor-suppressor miRNA)

Advantages

  •  Multiple-target suppression for RAS, KRAS signal network (AKT and ERK) and SOS1
  • Artificially modified nucleic acid optimized to increase RNase degradation resistance of miR-143
  • Anti-tumor activity at low concentration   ex.) DLD-1  IC50 : 1.32nM
  • Synergetic anti-tumor effect for KRAS mutated cancer by combination therapy with EGFR inhibitor, Cetuximab

Background and Technology

miR-143 is localized on chromosome 5q32, frequently under-expressed in variety of cancer and suggested involvement with cancer as tumor suppressor miRNA. miR-143 has been reported not only silencing total RAS, but also its downstream, effector signal molecules ERK and AKT and expressing synergetic suppressive effect.
Inventors found that miR-143#12 which was originally designed and modified based on the natural human miR-143 showed strong anti-tumor effect. As a background of high activity, it is suggested that miR-143#12 has excellent RNase resistant and remained long-term activity.
The effect of miR-143#12 in vitro has been proved and we demonstrated that human tumor cell line xenografted nude-mouse i.v. administrated miR-143#12 showed a remarkable anti-tumor effect at a low dose in all cases (Colon cancer, Bladder cancer, Gastric cancer, Kidney cancer, Rhabdomyosarcoma). For animal injection, miRNA‐143#12 was loaded in polyionic copolymers (PIC) to deliver miRNA to the tumors, but the delivery system is not limited to PIC.

Left: Sequences of synthetic miR-143 used in this study.
F RNA; Fluoro-RNA, Ome RNA; O-Methyl RNA, PS; phosphorothioate

Right: Remaining percentage of each miR‐143, Am, #1 and #12, remaining in the presence of FBS evaluated by performing RT‐qPCR. The 0‐min value of each miR‐143 is indicated as 100%. The mean value was taken for each time.

Data

Effect of miRNA 143#12 single and c ombination with Cetuximab (Erbitux)

Patent

JP6730717, US16/092,830, EP3444345, CN109477090A

Publications

Rhabdomyosarcoma   
Cancers 2020, 12(11), 3312.
https://doi.org/10.3390/cancers12113312
Colon cancer
Cancer Sci. 2018 May;109(5):1455-1467.
https://doi.org/10.1111/cas.13559
Bladder cancer
Mol Ther Methods Clin Dev. 2019 Feb 20;13:290-302.
https://doi.org/10.1016/j.omtm.2019.02.005
Gastric cancer
J Mol Sci. 2019 Apr 5;20(7):1697.
https://doi: 10.3390/ijms20071697
Kidney cancer
Mol Ther. 2019 May 8;27(5):1017-1027.
https://doi.org/10.1016/j.ymthe.2019.03.004

Expectations

W e are looking for pharmaceutical or biotech companies who are interested in d evelopment new miRNA t herapeutics by using miR 143#12. We are happy to license or to provide miR-143#12 as a material sample for validation or obtaining data.
We would appreciate it if you could let us know your feedback.

Product No. ON-03809

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