A collaborative study between the Biozentrum of the University of Basel and Roche, published in Nature Communications, has revealed key factors that regulate the efficiency of intracellular transport of RNA drugs. Through a CRISPR/Cas9 genome-wide screen, the research found that slowing the transport of drugs within endosomes can significantly enhance the therapeutic efficacy of antisense oligonucleotide (ASO) therapies.

The researchers systematically analyzed the impact of thousands of genes on ASO activity and identified the AP1M1 gene as playing a critical role in the drug transport process. Dr. Liza Malong, a researcher at Roche, stated: "By modulating this gene, we can prolong the residence time of ASOs in endosomes, thereby increasing their chances of escaping and exerting their effects." Experimental data showed that this approach improves efficacy in both cell cultures and mouse models without requiring an increase in drug dosage.

Professor Anne Spang from the University of Basel noted: "This discovery not only provides new ideas for optimizing RNA therapies but its principles may also be applicable in the field of anti-infective treatments." The research team believes that these findings will drive the development of more effective treatment strategies for genetic diseases.