Nav: Home

RNA as a future cure for hereditary diseases

August 18, 2020

Short RNA molecules can be used as medication. Their effectiveness is based on the genetic information they carry: therapeutic RNA can bind to the body's own RNA and thus influence how it functions. However, only a handful of such drugs are available so far.

"That's mainly because it's tricky to get the RNA molecules to precisely the organ in the body where they need to take effect. Currently, that's the biggest hurdle in the development of RNA drugs," says Jonathan Hall, Professor of Pharmaceutical Chemistry at ETH Zurich. Together with Daniel Schümperli, Emeritus Professor from the University of Berne, and colleagues from ETH, University Hospital Zurich and Triemli Hospital Zurich, he has now succeeded in developing an RNA molecule that can compensate for the effect of gene mutations in bone marrow cells.

This therapeutic approach could one day be applied to a rare hereditary disease called erythropoietic protoporphyria (EPP), which affects people whose mother and father both have a genetic predisposition to the disease. Those who suffer from EPP experience a painful sensitivity to sunlight.

Gene mutations cause the body of these patients to produce less of a certain enzyme, ferrochelatase. Ferrochelatase is central to the production of haemoglobin, the protein that transports oxygen in the blood and makes it appear red. This ferrochelatase deficiency causes a metabolic molecule, protoporphyrin, to accumulate in the red blood cells. Protoporphyrin reacts to rays of visible light, forming molecules that attack tissue and can cause painful inflammation when the patient is exposed to sunlight or a strong artificial light.

Fusion molecule shown to be effective

Hall and his colleagues developed several short RNA molecules, which bind to the RNA copy of the ferrochelatase gene in the body's cells. In cell culture experiments, they identified certain molecules that were able to restore a sufficient production of the enzyme and thus compensate for the negative effects of the known EPP gene mutations.

However, developing the RNA molecule was only the first part of the task. "This molecule must also be able to reach the right organ in the body and from there penetrate the interior of the cells," Hall says. In the case of EPP, these are the blood stem cells in the bone marrow. To this end, the researchers fused one of the RNA molecules with various chemically active compounds, which they tested in a mouse model of EPP. They identified one fusion molecule - the RNA molecule fused with cholesterol - that was able to compensate for the gene mutation in this animal model.

Research not yet complete

Hall stresses that it is too early to label the molecule he has identified as an RNA drug. In demonstrating that such molecules can be used to increase the amount of functional ferrochelatase in mice, the researchers are at only an early stage of their work. "This is the first step and it shows that our approach holds promise," Hall says. Next, the researchers need to optimise the fusion molecule or identify other fusion molecules that are even more effective, he explains, adding that they also require additional, more refined mouse models for the EPP disease. Further research is essential to find an optimum drug candidate whose effect can then be investigated in humans.
This study was carried out with funding support from the National Center of Competence in Research (NCCR) RNA & Disease.


Halloy F, Iyer PS, ?wiek P, Ghidini A, Barman-Aksözen J, Wildner-Verhey van Wijk N, Theocharides APA, Minder EI, Schneider-Yin X, Schümperli D, Hall J: Delivery of oligonucleotides to bone marrow to modulate ferrochelatase splicing in a mouse model of erythropoietic protoporphyria. Nucleic Acids Research 2020, 48: 4658-4671, doi: 10.1093/nar/gkaa229

ETH Zurich

Related Bone Marrow Articles:

Nanoparticles can turn off genes in bone marrow cells
Using specialized nanoparticles, MIT engineers have developed a way to turn off specific genes in cells of the bone marrow, which play an important role in producing blood cells.
How stress affects bone marrow
Researchers from Tokyo Medical and Dental University (TMDU) identified the protein CD86 as a novel marker of infection- and inflammation-induced hematopoietic responses.
3D atlas of the bone marrow -- in single cell resolution
Stem cells located in the bone marrow generate and control the production of blood and immune cells.
Dangerous bone marrow, organ transplant complication explained
Scientists have discovered the molecular mechanism behind how the common cytomegalovirus can wreak havoc on bone marrow and organ transplant patients, according to a paper published in the journal Cell & Host Microbe.
Viagra shows promise for use in bone marrow transplants
Researchers at UC Santa Cruz have demonstrated a new, rapid method to obtain donor stem cells for bone marrow transplants using a combination of Viagra and a second drug called Plerixafor.
Bone marrow may be the missing piece of the fertility puzzle
A woman's bone marrow may determine her ability to start and sustain a pregnancy, report Yale researchers in PLOS Biology.
Cells that make bone marrow also travel to the womb to help pregnancy
Bone marrow-derived cells play a role in changes to the mouse uterus before and during pregnancy, enabling implantation of the embryo and reducing pregnancy loss, according to research published Sept.
Uncovering secrets of bone marrow cells and how they differentiate
Researchers mapped distinct bone marrow niche populations and their differentiation paths for the bone marrow factory that starts from mesenchymal stromal cells and ends with three types of cells -- fat cells, bone-making cells and cartilage-making cells.
Zebrafish help researchers explore alternatives to bone marrow donation
UC San Diego researchers discover new role for epidermal growth factor receptor in blood stem cell development, a crucial key to being able to generate them in the laboratory, and circumvent the need for bone marrow donation.
New material will allow abandoning bone marrow transplantation
Scientists from the National University of Science and Technology 'MISIS' developed nanomaterial, which will be able to restore the internal structure of bones damaged due to osteoporosis and osteomyelitis.
More Bone Marrow News and Bone Marrow Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: The Power Of Spaces
How do spaces shape the human experience? In what ways do our rooms, homes, and buildings give us meaning and purpose? This hour, TED speakers explore the power of the spaces we make and inhabit. Guests include architect Michael Murphy, musician David Byrne, artist Es Devlin, and architect Siamak Hariri.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

What If?
There's plenty of speculation about what Donald Trump might do in the wake of the election. Would he dispute the results if he loses? Would he simply refuse to leave office, or even try to use the military to maintain control? Last summer, Rosa Brooks got together a team of experts and political operatives from both sides of the aisle to ask a slightly different question. Rather than arguing about whether he'd do those things, they dug into what exactly would happen if he did. Part war game part choose your own adventure, Rosa's Transition Integrity Project doesn't give us any predictions, and it isn't a referendum on Trump. Instead, it's a deeply illuminating stress test on our laws, our institutions, and on the commitment to democracy written into the constitution. This episode was reported by Bethel Habte, with help from Tracie Hunte, and produced by Bethel Habte. Jeremy Bloom provided original music. Support Radiolab by becoming a member today at     You can read The Transition Integrity Project's report here.