Advantages of gene activation by nuclear microRNAs

Activation of the endogenously expressed gene, such as VEGFA, by naturally existing nuclear microRNAs, has several advantages over traditional means of increasing the expression of a therapeutic gene:

1.

By upregulating the cell´s own gene, all spliceforms of a gene are equally activated and therefore more natural biological response is achieved. In traditional gene therapy approaches, typically only one spliceform is delivered to the target cell.

2.

As compared to canonical miRNAs used for gene silencing, target abundance is much lower, and therefore lower quantity of miRNA is needed for biological response.

3.

Target gene upregulation is caused by epigenetic modifications in the gene promoter. Therefore, upregulation is long-lasting but subject to silencing in the future if epigenetic pressure favors silencing.

4.

In traditional gene therapy, a cDNA is typically delivered with viral vectors which have safety concerns and immunogenic properties. MicroRNA delivery can be performed by engineered exosomes or novel non-viral methodologies such as liposomes or tissue targeting peptides.

5.

Unlike much larger mRNA-drugs which are relatively unstable and induce immunological responses, miRNAs have “stealth”-properties being more stable and less recognized in target cells. Therefore, these miRNAs can be readministered for the patient.

MARKET POTENTIAL

HEART FAILURE

The aging population drives the heart failure market. The incidence, prevalence, and therapeutics costs are increasing in the future. Currently available treatments are not effective enough for the growing healthcare problem. The heart failure drug market is expected to reach $11.8 Billion by 2025 (13.7% CAGR). Societal demand is very high since medical spending in the USA alone is more than $40 billion today. Efficient treatment for heart disease opens up the multi-billion market potential for the company able to bring such treatment to the market.

PERIPHERAL ARTERY DISEASE

The global Peripheral Artery Disease Market was valued at $3,136 million in 2016 and is estimated to reach $5 billion by 2023, growing at a CAGR of 6.8% from 2017 to 2023. Peripheral artery disease is a circulatory disease in which plaque builds up in the arteries carrying blood from the heart of the patient to the legs and arms. An increase in the incidence of the population suffering from diabetes and high blood pressure, which poses a high-risk factor for peripheral artery disease, drives the market growth. Also, favorable reimbursement scenarios for peripheral artery disease treatment and the introduction of advanced treatments boost the market growth.

INTELLECTUAL PROPERTY 

RNatives has PCT and national patents pending for microRNA that upregulates VEGFA gene expression.