Róbert Langer

Engineering Steric‐Hindrance‐Guided Crystalline Vacancies in a Scalable Pillared‐Layer Nickel‐MOF for Efficient Gas Uptake and Separation

Engineering local vacancies in metal–organic frameworks (MOFs) presents a promising route to high‐performance gas adsorption/separation, yet conventional defect engineering often yields statistically distributed vacancies. Here, we report a steric‐hindrance‐programmed strategy to construct periodically ordered vacancies in pillared‐layer LIFM‐Ni‐3‐H 2 O via de novo synthesis by changing pyrazine linkers in a full‐pillared reference TJE‐1 to bulkier triethylenediamine ligands, resulting in missing‐pillars to produce potential vacancies in a regularly staggered interlayer fashion. Single‐crystal x‐ray diffraction unambiguously identifies the alternating pillar/vacancy arrangement, and digestion 1 H NMR supports overall stoichiometry. Removing capped water molecules converts LIFM‐Ni‐3‐H 2 O into LIFM‐Ni‐3 with complete exposure of the open‐metal Ni 2+ ‐sites, reshaping the local pore to form a contracted Window‐I and an enlarged Window‐II bearing open‐metal sites for molecular accessing and binding. LIFM‐Ni‐3 enables efficient separation processes: adsorbing SF 6 at Window‐II with 2.64 mmol g −1 uptake at 0.1 bar while excluding N 2 , and purifying CH 4 by removing minor C 2 H 6 /C 3 H 8 from natural gas with an exceptional productivity of 13.5 mmol g −1 . This represents a rare example that features simultaneously high capacity and selectivity by overcoming capacity–selectivity trade‐off, and combines favorable low‐pressure capture with fast apparent uptake responses. The scale‐up experiment testifies reliability of this pillar‐displacing approach for mass production and scalable gas separation.

Accelerated discovery of thermostable mRNA–lipid nanoparticle vaccines using data-efficient AI

The instability of mRNA-lipid nanoparticles (LNPs) necessitates ultra-cold storage, limiting global distribution and their broader application in advanced delivery systems. Solid-state, water-free formulations enhance thermostability and enable integration into emerging delivery modalities such as microneedle patches. Previous efforts to stabilize mRNA-LNPs have been constrained by narrow formulation scope and low-throughput screening methods. Here we introduce Algorithm-Guided Experimental design for lipid Nanoparticle Thermostabilization (AGENT), an artificial intelligence (AI)-driven framework that couples high-throughput experimentation with Bayesian optimization to identify thermostable mRNA-LNP formulations. AGENT extracts maximal information from sparse experimental datasets, enabling efficient formulation optimization in six iterations completed within 1 month. We stabilized mRNA vaccines with two clinically relevant LNPs representative of the Moderna (SM-102-based) and Pfizer-BioNTech (ALC-0315-based) compositions into solid-state formulations that retained 100% bioactivity after storage at 37 °C for more than 2 months. In rodents and non-human primates, thermostable, solid-state vaccine formulations induced antigen-specific immune responses non-inferior to those elicited by intramuscular delivery of freshly prepared soluble vaccines.

An ingestible origami-inspired metamaterial for prolonged oral delivery of therapeutics

A modular hydrogel system with independent control of bioadhesion, fibrosis, and stiffness

Demonstrates independent control of bioadhesion and stiffness in soft tissues, suggesting a new path for functional implant design.

The Use of Deep Learning in RNA Therapeutic Development

Review examines deep learning usage to optimize RNA therapeutics, highlighting challenges and future directions.

Positioning hydrogels for next-generation immunovirotherapy in glioblastoma

High-grade gliomas, including Glioblastoma (GBM), are the most common primary malignant tumor of the central nervous system and confer a dismal clinical prognosis. Current standard-of-care consists of maximal safe resection followed by radiation, chemotherapy, and/or tumor treating fields. Immunovirotherapy is a novel treatment modality in which oncolytic viruses (OVs) are engineered to induce oncolysis and concurrently stimulate an antitumor immune response. Presently, effective OV delivery is challenged by the complex tumor microenvironment and the blood-brain barrier. Hydrogels have shown promise in overcoming such challenges; built of natural and synthetic polymers, hydrogels can effectively deliver therapeutic payloads over an extended period. Hydrogels may also help facilitate OV augmentation with immune adjuvants such as checkpoint inhibitors. In this review, we 1) summarize advances and challenges in OV therapy; 2) describe how hydrogels can improve delivery of viral therapies; and 3) highlight opportunities for hydrogel-mediated OV–immune adjuvant combinations in the treatment of GBM and other high-grade brain tumors. Glioblastoma is an aggressive brain tumor with poor prognosis; while treated with surgery and therapy, immunovirotherapy faces delivery barriers that hydrogels may help overcome. Here, the authors summarize progress in oncolytic virus therapy, hydrogels for delivery, and their combination with immune therapies.

The critical role of food fortification in combatting malnutrition and disease susceptibility in Africa

Malnutrition can severely compromise immune function, rendering populations more vulnerable to both communicable and non-communicable diseases. Here, we discuss food fortification and micronutrient supplementation programs that have been instrumental in mitigating malnutrition across Africa and in controlling disease spread, marking considerable advances in public health throughout the continent. Jaklenec, Yang et al. examine how malnutrition heightens disease susceptibility in Africa. They comment on the successes of food-fortification efforts to date and outline remaining barriers and future directions.

Accelerating discoveries in cancer nanomedicine using AI

The integration of artificial intelligence (AI) into cancer nanomedicine is transforming personalized therapy and diagnostics. Focusing on AI-guided design and optimization of nanomedicines, we evaluate how computational technologies can be used to improve targeting precision and therapeutic efficacy by matching treatments to each patient’s genetic and phenotypic profile. Surveying contemporary research, this Perspective presents a multidimensional view of AI-enabled nanomedicine that captures its technological, biological, and clinical complexity. Probabilistic and mechanistic models now facilitate the real-time adaptation of nanoparticle formulations. Looking ahead, we anticipate that AI will accelerate discovery and help nanomedicine realize its full potential in precision oncology. In addition to reviewing recent advances, we propose concrete guidelines for embedding AI throughout the nanomedicine pipeline, spanning data curation, model development, preclinical validation, and clinical translation. Finally, we highlight persistent gaps in standardized datasets, model interpretability, and regulatory alignment that must be addressed to achieve widespread clinical impact. Artificial intelligence is set to transform precision oncology by addressing challenges in targeting, efficacy, and therapeutic personalization. Its integration into cancer nanomedicine accelerates clinical translation by unifying technological, biological, and clinical complexities, enabling the design of nanoparticle therapies tailored to individual patient profiles.

Wafer-Scale Laser-Writing of Nanoporous Membranes with Monodisperse Pores for Robust Immunoisolation

Membranes that prevent cellular infiltration are essential components of immune-isolation devices. Stringent pore size control is critical to robustly exclude immune cells while preserving the efficient transport of nutrients and therapeutic molecules. Conventional membrane fabrication methods, however, struggle to balance these two properties. For instance, phase separation and fiber spinning generate highly tortuous pores that restrict diffusion, while random pore overlaps due to ion track etching result in oversized defects that compromise immune isolation. Here, we leverage scalable laser-writing tools to achieve spatially controlled open-through and dense pores with uniformly distributed submicrometer sizes for rapid transport and robust immune cell exclusion. Given the optical limits of laser aligners when fabricating submicrometer features, we tuned substrate reflectivity and exposure parameters to overcome these resolution limits. Self-standing and flexible membranes were achieved via thickness-tunable grid layers supporting membrane mechanical integrity. We report pore sizes as small as ca . 600 nm (below the resolution limits of the laser exposure systems) and over 20% open area at the exposure times of ∼3 min/cm 2 . Compared with conventional methods, this approach minimizes pore tortuosity, narrows the pore distribution, and improves the open pore density. Enhanced pore control is highlighted by macrophage infiltration studies, which indicate that these membranes reliably exclude macrophages at nominal pore sizes greater than those previously achievable. This approach thus provides a scalable pathway toward next-generation immunoisolation membranes for enhanced implantable therapeutic devices.

Activation of the coagulation cascade as a mechanism for selective nanoparticle-mediated RNA delivery to the endothelium in vivo

Investigates RNA delivery to endothelium in vivo using coagulation-modified nanoparticles, suggesting targeting improvements.

Engineered 3D immuno-glial-neurovascular human miBrain model

Observational analysis reveals tau pathology in Alzheimer's model derived from patient stem cells, indicating novel insights into disease mechanisms.

Enhanced macromolecule bioavailability in rats and pigs using an in situ forming synthetic epithelial lining

Oral delivery of macromolecules is hindered by enzymatic degradation, poor epithelial permeability, and rapid gastric transit, leading to low bioavailability. Existing permeation enhancers (PEs), such as salcaprozate sodium and sodium caprate, improve absorption but do not fully address proteolytic degradation and require high doses due in part to short gastrointestinal residence times. We developed the Peroral Mucosal Epithelium Absorption Enhancer (PERMEATE) system, an orally administered polymer film designed to adhere to the small intestinal mucosa, maximizing contact between therapeutics, PEs, and the absorptive tissue. Utilizing Synthetic Tissue-Lining (SYNT™) technology, PERMEATE triggers endogenous catalase-dependent dopamine polymerization to form an in situ polydopamine coating, creating a temporary depot that enhances co-localization and prolongs exposure to the absorptive mucosa. We assessed PERMEATE's potential to enhance the oral bioavailability of semaglutide (SEMA). High-throughput screening using the GI tissue robotic interface system (GI-ORIS) identified glycocholic acid (GCA) and ammonium carbonate (NHCO) as effective PEs when combined with SYNT. Ex vivo studies ( n = 8–24) and in vivo tests in Sprague-Dawley rats ( n = 5–11/group) demonstrated a 200-fold increase in bioavailability compared to SEMA alone ( P = 0.0001) and a 6-fold increase relative to SEMA+PE without SYNT ( P = 0.0011). In Yorkshire pigs ( n = 3–4), PERMEATE achieved a 2.4 % absolute bioavailability, a 6-fold improvement over SEMA+PE controls ( P = 0.0316). These results suggest PERMEATE as a promising platform for improving oral macromolecule delivery through enhanced mucosal adhesion and prolonged therapeutic contact, supporting further development for clinical application. • An in situ forming synthetic epithelial lining (SYNT) improves intestinal retention and absorption of macromolecules. • PERMEATE platform achieves 200-fold and 6-fold semaglutide bioavailability improvement in rats and pigs, respectively. • Co-formulation with permeation enhancers and SYNT enables tunable, scalable oral delivery of peptide therapeutics.

Inflammatory reprogramming of human brain endothelial cells compromises blood-brain barrier integrity in Alzheimer's disease

Observational analysis reveals how inflammation compromises blood-brain barrier in Alzheimer's disease, suggesting NF-KB as a therapeutic target.

Improving Health and Safety in Welding Through Remote Human–Robot Collaboration

The remote-controlled welding system improves weld integrity and worker safety, indicating significant industrial potential.

Vascular-Perfusable Human 3D Brain-on-Chip

This research demonstrates a 3D brain-on-chip system incorporating multiple cell types, suggesting enhanced modeling of neurological diseases.

Engineered prime editors with minimal genomic errors

Prime editors make programmed genome modifications by writing new sequences into extensions of nicked DNA 3′ ends1. These edited 3′ new strands must displace competing 5′ strands to install edits, yet a bias towards retaining the competing 5′ strands hinders efficiency and can cause indel errors2. Here we discover that nicked end degradation, consistent with competing 5′ strand destabilization, can be promoted by Cas9-nickase mutations that relax nick positioning. We exploit this mechanism to engineer efficient prime editors with strikingly low indel errors. Combining this error-suppressing strategy with the latest efficiency-boosting architecture, we design a next-generation prime editor (vPE). Compared with previous editors, vPE features comparable efficiency yet up to 60-fold lower indel errors, enabling edit:indel ratios as high as 543:1. Engineered prime editor systems with reduced occurrences of unwanted insertions or deletions during genome editing are developed.

Biotechnology in materials science: A storied past and a bold future

Review highlights transformative biomedical innovations at the interface of biotechnology and materials science, suggesting expansive potential in organ bioprinting and personalized medicine.

Gastrointestinal neuroprosthesis for motility and metabolic neuromodulation

Closed-loop neuromodulation improves GI tract motility in swine models, suggesting a novel treatment for dysmotility.

IL-17A neutralization fails to reduce pulmonary or renal vasculitis in experimental autoimmune vasculitis.

IL-17A neutralization alone is not efficacious in ameliorating pulmonary and renal vasculitis in an experimental autoimmune vasculitis rat model, despite the major participation of Th17 cells.

Stable Natural Iron Complex Micronutrient Powder for Enhanced Cellular Uptake

In vitro study demonstrates enhanced iron bioaccessibility and cellular uptake in intestinal cell models, highlighting FeC-4-1 as an effective food fortificant.