* The European Federation of Crohn's & Ulcerative Colitis Associations (EFCCA)

CELL NUCLEUS

Inflammatory bowel diseases (IBDs) are a group of conditions characterized by the chronic inflammation of the gut. Globally, over 10 million people live with IBD. That includes over 3 million people in Europe*.

The mRNA is just a copy of the original instructions that are within the DNA, encoded in the genes.

The number of prevalent cases is higher in females (3,9 million) than males (3 million).** IBDs are diagnosed most frequently in young adults, between 15 and 35 years old.*** Although there is no cure for IBD, its symptoms can be minimized by following medical management.

WHY THIS PROJECT?

GENE

** The global, regional, and national burden of IBDs in 195 countries and territories, 1990-2017: a systematic analysis for the GBD 2017 *** Crohn’s and colitis foundation centre for diseases control and prevention (CDC)

ULCERATIVE COLITIS (UC)

Affects only the large intestine and the inflammation is located in the inner lining of the gut.

siRNAs are small pieces of RNA that can bind to the mRNA, degrade it and block de production of proteins. As it “silences” the message and disrupts the process it is called gene silencing. Our therapy uses siRNA molecules that silence JAK1 and JAK3 genes. This way, the proteins will not be produced within immune cells. Those cells are not activated and the inflammation is reduced.

CROHN’S DISEASE (CD)

Affects any part of the digestive system and the inflammation may involve all gut layers.

siRNA

siRNA binds the mRNA. The mRNA is destroyed by the cell.

THE RESPONSIBLE MOLECULES

As JAK1 and JAK3 are present in other cells of our organism, to avoid side-effects, we need to take this cure directly to the intestine.

MICROCAPSULE Loaded with nanolipid carriers

INTESTINAL EPITHELIUM

▉ High incidence ▉ Low incidence

INTESTINAL VILLUS

INTESTINAL CELLS

The most common forms of IBD are ulcerative colitis (UC) and Crohn’s disease (CD). The main difference between them is the area of the digestive system that they affect.

NANOLIPID CARRIER Transporting and protecting siRNA.

The production of JAK1 and JAK3 is blocked.

INMUNE CELLS AND INFLAMMATORY MOLECULES

siRNA

Researchers have discovered two proteins responsible for the activation of immune cells, named JAK1 and JAK3. Thus, they are two potential targets for treatments: if we can stop them from forming, then the inflammation process is hindered.

JAK1 and JAK3

SWITCHING OFF THE PROCESS

To synthesize these proteins, our body has certain molecular tools. One of them is the mRNA, a genetic molecule that contains the instructions for the cellular protein factories called ribosomes.

mRNA

RIBOSOME

mRNA

DNA (JAK GENE)

With the information to build the protein

The immune cells that migrate to the intestine produce molecules that activate more immune cells, in a feedback loop that damages the tissue.

INFLAMMATION OUT OF CONTROL

siRNA molecules are very fragile. For this, we have designed nanocarriers made of highly stable lipid particles with a good safety profile. They protect the siRNA all the way through the gut and ensure it reaches the target cells.

NANOCARRIERS

Our final objective is to achieve an oral formulation of the treatment, safe and effective, that is compatible with patients’ daily life.

NEW DEAL AIM

IBD INTESTINE

It occurs mainly due to the wrong functioning of some cells of the patient’s immune system, that start to react against their own intestine causing the inflammation and, as a consequence, the tissue is damaged.

INFLAMMATION OUT OF CONTROL

ACTIVATED BY PROTEINS

WHAT CAUSES THE SWELLING?

INFLAMMATION OF THE TISSUE

It occurs mainly due to the wrong functioning of the immune system. Some cells of the patient’s immune system start to react against their own intestine causing the inflammation.

HEALTHY INTESTINE

siRNA Ready to bind and block the mRNA with the instructions for JAK1/JAK3 production

Nanocarriers are loaded into microcapsules that are able to transport the siRNA therapeutic throughout our digestive system.

MICROCAPSULES

The immune cells don't activate and the inflammation is reduced.

JAK-1 AND JAK-3 Target proteins responsible for gut inflammation

DELIVERING THE CURE

AT THE GENETIC LEVEL