Biotech & non coding RNAs

"RNA is the medicine of the future. It is time to study the code that allows predicting a function from an RNA sequence and translate this technology to the clinic.".

DR. PURI FORTES ALONSO

Microproteins, non-coding RNAs and antitumor biotechnology

Cells, especially tumor cells, evolve to produce thousands of different RNAs that fold into specific structures and bind to proteins, DNAs or other RNAs to perform functions that, sometimes, contribute to the malignancy of the cell. These RNAs, called non-coding, are unused therapeutic targets with enormous potential. If we manage to identify and block them, we will have treatments that prevent tumor malignancy and/or facilitate tumor destruction.

In the laboratory we study non-coding RNAs from three different aspects:

1. We identify RNAs that are produced in the most prevalent liver cancer: hepatocellular carcinoma. We study those that are essential for the survival of the tumor cell and that are related to the treatments that are currently used in the clinic, such as tyrosine kinase inhibitors, immunotherapy or chemo or radiotherapy. For example, NIHCOLE, an RNA that works like a staple that repairs DNA broken by radiotherapy. We think that blocking NIHCOLE while giving radiotherapy would increase the levels of broken DNA, leading to tumor cell destruction.

2. We identified RNAs from hepatocellular carcinoma and triple negative breast cancer that are capable of producing small proteins. We are interested in microproteins important for tumor generation and growth, because they would also be excellent therapeutic targets and drugs. In addition, we have found that many of them are tumor-specific. This allows us to develop vaccines against these tumors based on microproteins. RNA vaccines like COVID, but against cancer.

3. We can imitate the strategies that the cell uses to make these non-coding RNAs... in the laboratory! Using this, we have identified synthetic non-coding RNAs that, when introduced into the cell, are capable of controlling the levels of a therapeutic gene. If the gene is beneficial... great. If the gene produces unwanted side effects... with this RNA we can prevent the expression of the therapeutic gene until the patient recovers from the unwanted effects and can continue with the therapeutic treatment.

Puri Fortes. Directora del programa Biologia y Terapia de ARN. Cima Universidad de Navarra

GROUP LEADER

Dra. Puri Fortes
	+34 948 194 700 \| Ext. 814025
	pfortes@unav.es
	Research profile

Oncology research integrated in the
Cancer Center Clinica Universidad de Navarra

Learn about the cancer center

"Cellular stress dramatically modulates how Long non-coding RNAs is translated, and the integrated stress response is the Achilles heel of the cancer cell".

RNAs no codificantes terapéuticos y estrés integrado en Cáncer

We study long non-coding RNAs from 4 different aspects:

We identify long non-coding RNAs that are produced in the most prevalent liver cancer: hepatocellular carcinoma. We study those that are essential for the survival of the tumor cell and that are related to the treatments that are currently used in the clinic, such as tyrosine kinase inhibitors, immunotherapy or chemo or radiotherapy. For example, NIHCOLE, a long non-coding RNA that works like a staple that repairs DNA broken by radiotherapy. We think that blocking NIHCOLE while giving radiotherapy would increase the levels of broken DNA, leading to tumor cell destruction.

We identified long non-coding RNAs from hepatocellular carcinoma and triple negative breast cancer that are capable of producing small proteins. We are interested in microproteins important for tumor generation and growth, because they would also be excellent therapeutic targets and drugs. In addition, we have found that many of them are tumor-specific. This allows us to develop vaccines against these tumors based on microproteins. Long non-coding RNAs vaccines like COVID, but against cancer.

The strategies that the cell uses to make these long non-coding RNAs can be mimicked in the laboratory. For example, we have identified synthetic non-coding RNAs that, when introduced into the cell, are able to control the levels of a therapeutic gene. If the gene is beneficial... great. If the gene produces unwanted side effects... with this RNA we prevent its expression until the patient is well again and can continue with the treatment.

We also study how different states of cellular stress, especially that which triggers the so-called integrated stress response, impact the translation of microproteins. For example, we are seeing how if we decrease the ability of cancer cells to organize their stress response, the cell ends up completely changing its proteome and becomes more sensitive to immunotherapy.

Getting to know long non-coding RNAs better

This photo could represent a small primitive horse running. In reality, it is a picture of NIHCOLE obtained by atomic force microscopy. NIHCOLE is an RNA that acts as a staple to join DNA molecules broken by radiotherapy. Each image represents a single NIHCOLE molecule. When NIHCOLE binds to the DNA repair machinery, the image changes drastically.