Pipeline

MirNat is a start-up biotech company dedicated to development and production of high quality nutraceutical products containing plant microRNAs (from Moringa oleifera, Olea europaea and other Mediterranean medicinal plants) capable of inhibiting human cancers and fit for use in large varieties of nutritional medicinal purposes. In 2012, Zhang et al. reported that exogenous plant miRNAs are present in the sera and tissues of various animals and they are primarily acquired orally, through food intake. Functional studies in vitro and in vivo demonstrated that miR168a could inhibit LDLRAP1 expression in liver, and consequently decrease LDL removal from mouse plasma. These findings demonstrate that exogenous plant miRNAs in food can regulate the expression of target genes in mammals, evidencing for the first time a cross-kingdom regulation. Company’s mission is based on this innovative concept of “cross-kingdom functional sequence homology” between plant and mammalian microRNAs, where plant microRNAs explicit a regulation mechanism into the host mammalian cell, comparable to the endogenous one.

xxx-miR201234 -- Preclinical phase
xxx-miR201235 -- Preclinical phase
xxx-miR201236 -- Preclinical phase
mol-miR168 -- Preclinical phase
mol-miR159 -- Discovery

NB: miRNAs real names have been changed for patent restrictions.

MicroRNAs overview

MicroRNAs (miRNAs) are a class of about 20 – 24 nt small non-coding RNAs that can regulate their target gene expression transcriptionally and post-transcriptionally.

MicroRNAs biogenesis is a multi-step regulation mechanism that starts from the pri-miRNA, wrapped in hairpin-stem-loop secondary structure, and finishes with the mature miRNA, associated with the RISC Complex.

In animals, miRNAs can inhibit protein translation. The not complementary miRISC-mRNA interaction into the seed region, creates a steric obstruction that inhibits the ribosomes attachment to the mRNAs. In plants, miRNAs can allow target mRNA cleavage. In this case, the miRISC-mRNA interaction is complete into the seed region.

Many plant miRNAs are evolutionarily conserved from species to species within the same kingdom. Identical miRNA sequences exist in closely and distantly related plant species, with little apparent effect of phylogenetic distance. These indicate that miRNA sequences are highly conserved across great phylogenetic distances and that similar selection pressures have been active in the regulation of gene expression in plant cells since the earliest stages of their evolution. Not only are miRNA genes conserved across all plant lineages, but we also observed that their targets are conserved in different plant families. Although there are many nucleotide changes among the targets of different plant species, the sequences of the complementary sites are highly conserved.

24 nucletoides, infinite roles

Development of cancer involves combined interaction of both tumour suppressors and cancer inducers. MiRNAs may function as a novel class of both oncogenes and tumour suppressor genes. The miRNAs with increased expression in tumours are thought to function as oncogenes and are termed as oncomirs. These oncomirs negatively inhibit tumour suppressor genes and/or those controlling cell differentiation or apoptosis and thereby promote tumour development. In contrast, some miRNAs exhibit decreased expression in cancer cells and are considered tumour suppressor miRNAs. Tumour suppressor miRNAs usually prevent tumour development by negatively inhibiting oncogenes and/or genes that control cell differentiation or apoptosis.

The miRNAs and small interfering RNAs (siRNAs) are used to treat cancer by targeting specific protein by inhibiting their counterpart mRNA in mechanism of proliferation, invasion, anti-apoptosis, drug resistance, and metastasis. The delivery of RNA-based therapeutics for cancer therapy still remains a daunting task. Effective delivery of candidate genes to specific cell types is perhaps the biggest challenge in the field of gene therapy.

Cardiovascular diseases are the leading cause of morbidity and mortality in developed countries. The pathological process in the heart is associated with an altered expression profile of genes that are important for cardiac function. MiRNAs are important for normal heart function and development; these RNA molecules have an important function during neovascularization and vascular remodelling.  Several miRNAs were shown to take part in the pathogenesis of coronary artery disease (CAD) and atherosclerosis; in addition, evidence suggest that miRNAs might have important roles as diagnostic and prognostic biomarkers of cardiovascular disease and novel therapeutics agents.

The response to pathogens is governed by the complex interactions and activities of the large number of diverse cell types involved in the immune response. The white blood cells of the immune system derive ultimately from the progenitor or precursor cells—the hematopoietic stem cells in the bone marrow. In hematopoietic cells, miRNA levels are dynamically regulated during lineage differentiation but also during the course of the immune response (abnormal expression of miRNAs has been reported during inflammation). miRNA-dependent alterations in gene expression in hematopoietic cells are critical for mounting an appropriate immune response to a wide range of pathogens, spontaneously emerging tumours and autoimmune cells. Deregulation of hematopoietic-specific miRNA expression results in defects in both central and peripheral tolerance, hematopoietic malignancies, and sometimes both. All these evidence identify miRNAs as critical targets for immunomodulatory drug development

+ miRNAs and cancer therapy

Development of cancer involves combined interaction of both tumour suppressors and cancer inducers. MiRNAs may function as a novel class of both oncogenes and tumour suppressor genes. The miRNAs with increased expression in tumours are thought to function as oncogenes and are termed as oncomirs. These oncomirs negatively inhibit tumour suppressor genes and/or those controlling cell differentiation or apoptosis and thereby promote tumour development. In contrast, some miRNAs exhibit decreased expression in cancer cells and are considered tumour suppressor miRNAs. Tumour suppressor miRNAs usually prevent tumour development by negatively inhibiting oncogenes and/or genes that control cell differentiation or apoptosis.

The miRNAs and small interfering RNAs (siRNAs) are used to treat cancer by targeting specific protein by inhibiting their counterpart mRNA in mechanism of proliferation, invasion, anti-apoptosis, drug resistance, and metastasis. The delivery of RNA-based therapeutics for cancer therapy still remains a daunting task. Effective delivery of candidate genes to specific cell types is perhaps the biggest challenge in the field of gene therapy.

+ miRNAs and cardiovascular diseases

Cardiovascular diseases are the leading cause of morbidity and mortality in developed countries. The pathological process in the heart is associated with an altered expression profile of genes that are important for cardiac function. MiRNAs are important for normal heart function and development; these RNA molecules have an important function during neovascularization and vascular remodelling.  Several miRNAs were shown to take part in the pathogenesis of coronary artery disease (CAD) and atherosclerosis; in addition, evidence suggest that miRNAs might have important roles as diagnostic and prognostic biomarkers of cardiovascular disease and novel therapeutics agents.

+ miRNAs and immune disease (allergy and infectious disease)

The response to pathogens is governed by the complex interactions and activities of the large number of diverse cell types involved in the immune response. The white blood cells of the immune system derive ultimately from the progenitor or precursor cells—the hematopoietic stem cells in the bone marrow. In hematopoietic cells, miRNA levels are dynamically regulated during lineage differentiation but also during the course of the immune response (abnormal expression of miRNAs has been reported during inflammation). miRNA-dependent alterations in gene expression in hematopoietic cells are critical for mounting an appropriate immune response to a wide range of pathogens, spontaneously emerging tumours and autoimmune cells. Deregulation of hematopoietic-specific miRNA expression results in defects in both central and peripheral tolerance, hematopoietic malignancies, and sometimes both. All these evidence identify miRNAs as critical targets for immunomodulatory drug development

Olea europea: an overview

The olive tree (Olea europaea L.) is one of the most economically important evergreen fruit crops in the Mediterranean countries. The olive oil has been declared as a healthy medicine for cardiovascular protection (“qualified health claim”) by the international recognized Food and Drug Administration (FDA) of the United States of America due to its protective effect against cardiovascular diseases. Olea europaea L. is widely studied for its alimentary use, the fruits and the oil are important components in the daily diet of a large part of the world’s population. Virgin olive oil, the fruit juice of this species, is worldwide appreciated due to its potential health and nutritional benefits, particularly given to the large number of phenolic compounds present in the olive tree. Olive leaves, available throughout the year, can be considered as a potential source of bioactive compounds; the oleuropein, hydroxytyrosol, verbascoside, apigenin-7-glucoside and luteolin-7-glucoside are the most abundant already identified in olive leaf extracts. The beneficial effects of olive oil and olive leaf extracts were already known in the ancient world, and scientifically investigated since the last couple of centuries, leading to a focus on their biological properties, including antioxidant activity, anti-HIV properties, anti-proliferative and apoptotic effects, protective effect against human leukemia, lipid-lowering activity, etc. Some of these properties have led to the inclusion in the European Pharmacopoeia (Ph. Eur.) of the 80% alcoholic extract of olive leaves , containing different bioactive compounds.

Moringa oleifera: the miracle tree

Moringa oleifera, one of the best known and mostly widely distributed and naturalized species of a monogeneric family Moringaceae, is considered one of the world’s most useful trees among all the medicinal plants, as almost every part of the tree can be used for food or other beneficial purposes. Moringa oleifera is a highly valued plant in tropic and subtropical countries where it is mostly cultived; it is an important food commodity which had enormous attention as the “natural nutritions of the tropics”. The leaves, fruit, flowers and immature pods of this tree are used as a highly nutritive vegetable in many countries. The leaves of this tree have attracted worldwide research interest because they are good source of natural antioxidants such as ascorbic acid, flavonoids, phenolics and carotenoids. The high concentrations of ascorbic acid, β-sitosterol, iron, calcium, phosphorus, copper, vitamins A, B and C, α tocopherol, riboflavin, nicotinic acid, folic acid, pyridoxine, β-carotene, protein and essential amino acids present in Moringa leaves make a valuable dietary supplement. A number of medicinal properties have been ascribed to various parts of this highly esteemed tree. Almost all the parts of this plant have been used for various ailments in the indigenous medicine of different countries, including the treatment of inflammation and infection diseases along with cardiovascular, gastrointestinal, hematological and hepatorenal disorders.