RNA Therapeutics

microRNA

Key regulator in epigenetics
As a target molecule of BIORCHESTRA’s leading project, the miR-485-3p contributes to lysosomal function, glial biology and cellular homeostasis by regulating CD36, SIRT1 and PGC-1α. For example, its expression level is abnormally increased in the post-mortem brain of the AD patients and in the plasma of the amyloid PET-positive MCI patients. Supporting this, overexpression of miR-485-3p leads to deficiency of the three said proteins, causing neurodegeneration and neuroinflammation.

BMD-001 comprises an antisense oligonucleotide (ASO) encapsulated by the BDDS™. Following cellular uptake, the ASO is released into the cytosol and binds to miR-485-3p, triggering its degradation. BMD-001 can not only suppress the activity of miR-485-3p but also reverse its effects. BMD-001 decreases neuroinflammation and promotes neurorestoration as well as clearance of pathological proteins. Thus, BMD-001 provides a solution to the underlying pathologies of many neuroinflammatory diseases including, but not limited to, AD, ALS and PD.

mRNA

Messenger of genetic information

BMRD-001 comprises a single mRNA sequence encoding iduronate 2-sulfatase (IDS) encapsulated by the BDDS™. Genetic mutations in the IDS gene that result in enzymatic deficiency lead to Hunter Syndrome (also known as MPS II), a rare genetic disease characterized by manifestations in the brain, skeletal, cardiac and respiratory systems. BMRD-001 (or BDDS:IDS mRNA) is developed to replace abnormal IDS proteins with functional ones; in particular, the BDDS™ ensures that drug reaches the brain and addresses neurological symptoms.