What are microRNAs?

MicroRNAs (miRNAs or miRs) are non-coding RNAs (ncRNAs) that regulate the expression of genes, usually through translational repression or mRNA degradation. Scientists have so far identified over 2,000 microRNAs and more than one-third of all human genes are predicted to be regulated by microRNAs. Since a single microRNA can regulate an entire network of genes, microRNAs operate as master regulators of the genome. Because levels of miRNAs are altered in many diseases, they can act as biomarkers for these diseases for the diagnosis, prognosis, prediction of response to therapy, and post- treatment monitoring. In addition, pathological changes caused by microRNA changes can potentially be reversed by microRNA-based therapy. Anti-miRs are oligonucleotides that inhibit microRNAs, and miR-mimics, double-stranded oligonucleotides increase microRNA function.

Watch the video below to learn more about microRNAs:

Since a single microRNA can regulate an entire network of genes, microRNAs operate as master regulators of the genome.

Approach to microRNA-based therapy

There are multiple approaches for microRNA-based therapy. One is microRNA-replacement therapy, in which an exogenous ‘‘microRNA mimic’’ for a microRNA with low levels of expression is introduced. Another approach is antimicroRNA therapy, in which a microRNA inhibitor for a microRNA that is overexpressed is introduced. These microRNA-modulating agents are synthetic oligonucleotides with sequences that are identical or complementary to the targeted microRNAs.

MicroRNAs expression patterns are altered in all types of cancer, with each cancer type displaying a distinctive signature microRNA expression pattern. A microRNA profile can therefore be an independent prognostic marker for cancer. In addition, it has been shown that changes in miRNAs can promote tumor development by increasing the expression of oncogenes that promote tumor growth and by decreasing the expression of tumor-suppressor genes. MicroRNAs have been linked to tumor development, invasion, metastasis, new blood vessel generation, and tumor resistance to chemotherapy and radiotherapy. Because microRNA mimics and antimiRs are sequence specific, compared to the conventional small molecule chemotherapy, fewer adverse sides effects are expected along with much greater probability of hitting their targets.

QTsome™ Delivery Platform Technology

> Platform Technology for Nucleic Acid Delivery with focus on microRNA (miRNA)/anti-miR (miR inhibitor)

> Combination of cationic lipids with tertiary and quarternary amine headgroups (QTsomes™)

> Tertiary amino-cationic lipids are conditionally ionizable and facilitate disruption of the lipid bilayer and oligonucleotide endosomal release under the acidic conditions of the endosome.

> Quarternary amino-cationic lipids are permanently charged, ensuring strong interaction between the lipids and the oligonucleotide, which ensures particle stability.

> Combination of Tert and Quart cationic lipids provide the optimum pH response profile that is not possible with each lipid individually.

> QTsomes™ are much more active than regular cationic liposomes in transfecting cells.

Increase in cationic charge density in response to pH