Researchers hit the target: they transport microRNAs against Muscular Dystrophy to muscle stem cells using nanoparticles

25.02.2025

MicroRNAs on nanoparticle vehicles are injected in model animals. Credit: Álvaro Somoza.

IMDEA Nanociencia researchers use nanoparticles as vehicles to deliver microRNAs to cells and treat Duchenne Muscular Dystrophy.
It is possible to specifically deliver the treatment to the muscle stem cells, avoiding accumulation in other organs

Madrid, 24th February 2025. In a collaboration between the IMDEA Nanociencia Institute (Madrid), Università Cattolica del Sacro Cuore (Rome), and the University of Bordeaux, researchers have made an important breakthrough in the therapeutic delivery of microRNAs against Duchenne muscular dystrophy, a disease with no cure, to date.

Duchenne muscular dystrophy is a genetic disorder characterized by the progressive loss of muscle mass, due to mutations in the dystrophin gene. Without the corresponding functional protein, muscles cannot function or repair themselves properly, resulting in the deterioration of skeletal, heart, and lung muscles. Because the dystrophin gene is located on the X chromosome, it mainly affects males, while females are usually carriers.

Researchers have developed a strategy to treat muscular dystrophy, which uses nanoparticles as vehicles to transport therapeutical microRNAs to muscle stem cells. Once inside the muscle stem cells, the nanoparticles release the microRNA to stimulate the production of muscle fibers.

MicroRNA is a class of RNA molecules that play a crucial role in gene regulation. The delivery of microRNAs through the bloodstream is complicated, due to low stability and penetration. In this context, nanoparticles act as safe biocarriers and improve the delivery of this therapy.

In their work, the researchers developed an aptamer, a molecule that selectively recognizes specific other molecules, in this case, proteins that are in muscle stem cells. By combining the aptamer with a nanoparticle, they were able to release the microRNA on muscle stem cells with great precision, and reactivate muscle regeneration.

Researchers have reported the activity of the system in cellular and animal models, where they have observed not only muscle regeneration at the cellular level, but recovery at the functional level. The muscles of the treated mice improved, they were stronger after the treatment, and thus enhanced the mice's functional capacity.

Therapeutic molecules hit the target

Generally, when a nanoparticle is administered intravenously, it usually accumulates in the liver, or in the kidneys, depending on its size. In addition, in this process, the nanostructure is coated with proteins from the plasma – it is the so-called protein corona, which modulates the biodistribution of the nanoparticle. These processes significantly affect where the nanoparticles accumulate, decreasing the effectiveness of the treatment.

In this study, nanovehicles modified with the aforementioned aptamer accumulate preferentially in muscles, and specifically in muscle stem cells, where they release microRNAs activating muscle regeneration.

Development of aptamers

Aptamers are DNA or RNA strands that adopt a specific three-dimensional structure, allowing them to bind with high affinity to target molecules. Their operation is similar to that of antibodies, which gives them wide potential as biosensors, and in therapies and diagnostics.

Looking for an aptamer that fits the desired therapeutic target is like looking for a needle in a haystack. To do this, an iterative process called SELEX (Systematic Evolution of Ligands by EXponential Enrichment) is often used, facilitating the selection of DNA or RNA sequences with high affinity for a target molecule. To do this, a random library of trillions of nucleic acid sequences is generated, and then incubated with the target molecule. It is likely that some of the chains in the library have an affinity for the target molecule. Then, a family of sequences with high affinity is selected through subsequent washes and amplification steps. Finally, the most efficient sequences are usually optimized for stability and functionality in therapeutic or diagnostic applications.

aptamer In their recent work, published in Nature Communications, the researchers conjugated nanoparticles with an aptamer against α7/β1 integrin, a very specific surface receptor expressed by muscle progenitors and differentiated myofibers that is virtually absent in other organs or tissues. In this way, it was possible for the aptamer-conjugated nanoparticles to efficiently target the muscles, with a high selectivity towards the muscle stem cells.

Álvaro Somoza, lead author of the study, is very enthusiastic about the results: "There are two very notable things to point out, first, the effective delivery of a microRNA to the desired organ, which increases the effectiveness of the therapy. On the other hand, this approach prevents the accumulation in other organs, such as the brain, kidneys or liver, which is key to prevent side effects. ."

The delivery platform for nucleic acids, such as microRNAS, developed by the team of. Prof. Somoza is biocompatible, non-toxic, and non-immunogenic, and can be easily adaptable for the release of oligonucleotides of different types for the treatment of various diseases.

The work is a collaboration between researchers at IMDEA Nanociencia (Madrid), led by Álvaro Somoza, Università Cattolica del Sacro Cuore (Rome), led by Daniela Palacios, and the University of Bordeaux, led by Jean-Jacques Toulmé. It is partially funded by the ERANET-EuroNanoMed (23360733) network, Ministry of Science, Innovation and Universidades (PID2023-146982OB-I00)land the Severo Ochoa Excellence accreditation granted to IMDEA Nanociencia (CEX2020-001039-S).

Glossary:

Nucleotide: the basic fundamental molecule of nucleic acids.
RNA: a macromolecule formed by a single chain of nucleotides that participates in essential biological processes for living beings together with DNA.
Oligonucleotide: short chain of nucleotides –nucleic acids, the building blocks of DNA or RNA. The length of the oligonucleotide is usually denoted by "-mer" (from Greek meros, "part"). For example, an oligonucleotide of six nucleotides is a hexamer.
Aptamer: Aptamers are molecules of artificial ssDNA, RNA, XNA, or peptide that bind a specific target molecule, or family of target molecules.
Muscle stem cells: also known as satellite or myosatellite cells, are a type of stem cells able to differentiate and fuse to augment existing muscle fibers. These cells are involved in the normal growth of muscle, as well as regeneration following injury or disease.

Reference:

Millozzi, F., Milán-Rois, P., Sett, A. et al. Aptamer-conjugated gold nanoparticles enable oligonucleotide delivery into muscle stem cells to promote regeneration of dystrophic muscles. Nat Commun 16, 577 (2025). https://doi.org/10.1038/s41467-024-55223-9

Link to IMDEA Nanociencia Repository:https://hdl.handle.net/20.500.12614/3828

Contact:

Álvaro Somoza
alvaro.somoza @imdea.org
NanoBiotechnology Group https://nanociencia.imdea.org/nanobiotechnology/group-home

Oficina de Divulgación y Comunicación en IMDEA Nanociencia
divulgacion.nanociencia [at]imdea.org

Source: IMDEA Nanociencia.

IMDEA Nanociencia Institute is a young interdisciplinary research Centre in Madrid (Spain) dedicated to the exploration of nanoscience and the development of applications of nanotechnology in connection with innovative industries.