Researchers at Karolinska Institutet have developed a method that permits environment friendly supply of therapeutic proteins and RNA to cells. The strategy, printed in Nature Communications, exhibits promising leads to animal research to ship gene editors and protein therapeutics.
The strategy is predicated on so-called extracellular vesicles (EVs), tiny bubbles which are naturally secreted by cells and may transport biologically energetic molecules between cells. Researchers have now succeeded in enhancing these bubbles by introducing two key elements: a small a part of a bacterial protein known as intein and a so-called fusogenic protein from a virus.
The fusogenic protein helps the bubbles to fuse with the endosomal membrane and launch their contents into the cell, whereas the intein can lower itself and thus assist launch therapeutic proteins contained in the cell.
“This modern engineering technique represents a serious step ahead for extracellular vesicle expertise, successfully overcoming key boundaries comparable to poor endosomal escape and restricted intracellular launch,” says Professor Samir EL Andaloussi, final creator of the examine and researcher on the Division of Laboratory Medication.
“Our in vivo findings spotlight the potential of engineered EVs as a flexible platform for delivering therapeutics to deal with a broad vary of situations, together with systemic irritation, genetic ailments, and neurological issues.”
The examine’s first creator, Dr. Xiuming Liang on the Division of Laboratory Medication, provides, “By enhancing the effectivity and reliability of therapeutic supply into goal cells, this expertise might considerably broaden the appliance of superior medicines.”
Mind modifications in mice
In experiments on cells and reside animals, the researchers had been capable of effectively ship Cre recombinase, a protein that may lower and paste DNA, and Cas9/sgRNA complexes, that are used to edit genes. When extracellular vesicles loaded with Cre recombinase had been injected into the brains of mice, a major change in cells within the hippocampus and cortex mind constructions was noticed.
“This offers hope to make use of the CRISPR/Cas9 gene scissors or related instruments to deal with extreme genetic ailments of the central nervous system, comparable to Huntington’s illness and spinal muscular atrophy,” says Liang.
The researchers additionally demonstrated that the approach might be used to deal with systemic irritation in mice.
Extra data: Xiuming Liang et al, Engineering of extracellular vesicles for environment friendly intracellular supply of multimodal therapeutics together with genome editors, Nature Communications (2025). DOI: 10.1038/s41467-025-59377-y. www.nature.com/articles/s41467-025-59377-y
