Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
Therapeutic extracellular vesicles produced at scale
This issue highlights the use of deep learning to detect anaemia from retinal fundus images, the local delivery of newly identified vasodilators for reducing ureteral contractions, a biomaterial-based vaccine to treat acute myeloid leukaemia, the reduction of the therapeutic dose of silencing RNA via its integration into extracellular vesicles, cellular nanoporation for the large-scale production of functional mRNA-encapsulating exosomes, anionic nanoparticles that enhance the intestinal permeability of orally delivered proteins, base editing in a mouse model of tyrosinemia, the optimization of the delivery of base editors, and a comparison of compatibilities in protospacer adjacent motifs and of on-target and off-target activities of SpCas9 variants.
The cover illustrates the production, via cellular nanoporation, of large quantities of extracellular vesicles loaded with endogenously transcribed therapeutic mRNAs and targeting peptides.
An injectable biomaterial vaccine encapsulating antigens associated with acute myeloid leukaemia, dendritic-cell-targeting pro-inflammatory cytokines and an adjuvant protects mice from the disease.
The therapeutic dose of small interfering RNA can be reduced by endogenously expressing and packaging the RNA into extracellular vesicles through its integration with the backbone of a highly enriched pre-microRNA.
Large quantities of extracellular vesicles produced via cellular nanoporation, and loaded with endogenously transcribed therapeutic mRNAs and targeting peptides, boost therapeutic outcomes in vivo.
Negatively charged nanoparticles of about 50 nm in size permit the oral delivery of insulin and other peptide drugs by temporally enhancing the permeability of the intestinal wall.
In an adult mouse model of tyrosinaemia, a base editor correcting an A-to-G splice-site mutation in the Fah gene restores the translation of the functional enzyme, promoting the repopulation of the liver with the corrected cells.
The overexpression of the transcription factor c-Jun improves chimeric-antigen-receptor T-cell functionality and enhances the killing of low-antigen-expressing liquid and solid cancers in mice.
Machine-learning algorithms trained with retinal fundus images, with
subject metadata or with both data types, predict haemoglobin concentration with
mean absolute errors lower than 0.75 g dl–1 and anaemia
with areas under the curve in the range of 0.74–0.89.
The local delivery of a calcium channel blocker and a Rho-kinase inhibitor, determined by screening for small molecules that cause ureteral relaxation, significantly reduce ureteral contraction in pigs.
A macroporous material encapsulating an immune-cell-activating cytokine, an adjuvant and tumour-associated antigens elicits prophylactic immunity to acute myeloid leukaemia in mice, and eradicates the disease when combined with chemotherapy.
Integrating silencing RNA into the backbone of a microRNA that is highly enriched in small extracellular vesicles reduces the therapeutic dose of the silencing RNA.
A cellular-nanoporation method produces large quantities of exosomes containing therapeutic mRNAs and targeting peptides that restore tumour-suppressor function in mice with orthotopically implanted phosphatase and tensin homologue (PTEN)-deficient brain gliomas.
Anionic nanoparticles increase intestinal permeability and enable the oral delivery of proteins, as shown with the delivery of insulin in healthy, hyperglycaemic, and diabetic mice.
Optimized adeno-associated viruses delivering split cytosine base editors and adenine base editors with trans-splicing inteins can edit brain, liver, retina, heart and skeletal-muscle tissues at therapeutically relevant efficiencies.
A comparison of compatibilities in protospacer adjacent motifs and of on-target and off-target activities of Streptococcus pyogenes Cas9 variants at endogenous sites in human cells enables the editing of new genomic sites associated with genetic diseases.
Intravenous delivery of an adenine base editor and a single-guide RNA for the Fah gene can correct an A>G splice-site mutation in an adult mouse model of tyrosinaemia.