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Many genetic therapies are limited by a lack of methods for delivering them to target cells in the body. We have developed technologies to engineer biological nanovesicles to load therapeutic proteins, target recipient immune cells and deliver Cas9 to knock out CXCR4 in primary human T cells.
We compared a range of linear and nonlinear models based on how accurately they could describe resting-state functional magnetic resonance imaging and intracranial electroencephalography dynamics in humans. Linear autoregressive models were the most accurate in all cases. Using numerical simulations, we demonstrated that spatiotemporal averaging has a critical and robust role in this linearity.
An intravenous needle that undergoes a temperature-responsive shape change by softening on insertion into the body may induce less trauma than commercial devices for intravenous access.
Base editors can restore the expression of survival motor neuron protein to therapeutically beneficial levels in animal and cell models of spinal muscular atrophy.
Barcoding cells with microparticles that emit near-infrared laser light enables the use of flow cytometry to track the dynamics of single cells by using more markers and fewer colours.
Leveraging the expertise of physicians to identify medically meaningful features in ‘counterfactual’ images produced via generative machine learning facilitates the auditing of the inference process of medical-image classifiers, as shown for dermatology images.
Patient-derived intestinal organoids and tumouroids supplemented with immune cells can be used to predict and study the on-target off-tumour toxicities of T-cell-engaging bispecific antibodies and to capture inter-patient variabilities in the responses to the antibodies.
DNA-based molecular computation allows for the simultaneous detection of multiple types of biomarker, as shown for the accurate identification of prostate cancer in serum samples on the basis of specific RNAs, proteins and small molecules.
Closed-loop spinal cord stimulation with commercially available electrodes can evoke sensations in the missing foot of three individuals with transtibial amputation, providing them with improved balance and gait and reducing phantom limb pain.
The targeted integration of large DNA payloads into primary human T cells can be efficiently achieved non-virally by leveraging Cas9-based editing and the DNA-repair pathway homology-mediated end joining.
We show that nonlinear latent factors and structures in neural population activity can be modelled in a manner that allows for flexible dynamical inference, causally, non-causally and in the presence of missing neural observations. Further, the developed neural network model improves the prediction of neural activity, behaviour and latent neural structures.
Nonlinear latent factors and latent structures in the activity of neural populations can be computationally modelled to enable flexible inference and to better predict neural activity and behaviour.
The growth of aortic aneurysms can be predicted via a dimensionless physiomarker, derived from first principles and calculated from data acquired via 4D flow magnetic resonance imaging, that describes a transition from stable blood flow to unstable aortic fluttering.
The composition of lipid nanoparticles for the delivery of tumour-antigen-encoding mRNA can be optimized via a screening method to enhance antitumour activity via the modulation of the immune activity of helper T cells.
Linear mathematical models derived from measurements of local field potentials and of whole-brain blood-oxygen-level-dependent neural activity predict resting-state neural dynamics at least as accurately as nonlinear models.
Antigen-restricted mature T cells can be generated from pluripotent stem cells edited to lack endogenous T cell receptors and class I major histocompatibility complexes by introducing the T cell selection components into the stromal microenvironment.
The optogenetic stimulation of pancreatic cholinergic signalling in insulin-deficient mice enhances the glucose-stimulated secretion of insulin and β cell proliferation.
A wide-field fluorescence microscope leveraging a spinning disc and high-speed cameras enables the recording of neural activities and neutrophil trajectories at micrometric resolution on curved cortical surfaces in live mice.
Optimized base editors targeting the exon-7 mutation in SMN2 restore expression of the survival motor neuron (SMN) protein to normal levels, as shown in mice with spinal muscular atrophy and in fibroblasts from patients with this genetic disease.