RNA Interference and Gene Delivery

Extrahepatic, cell-specific delivery of LNPs through competitive inhibition of ApoE-mediated uptake

This paper develops NanoPilot, a modular fusion protein platform to redirect lipid nanoparticles (LNPs) away from the liver and toward specific cell types, improving transfection efficiency in T-cells and reducing off-target uptake.

Mechanically-mediated low-pressure cell membrane poration enables tunable intracellular delivery of traditionally impermeable cargoes in high throughput and clinical scale formats

This paper introduces a mechanically-mediated low-pressure poration method for efficient, cargo-agnostic intracellular delivery with high throughput and clinical scalability.

pH-dependent anti-TfR1 NANOBODY(R) molecules deliver efficacious oligonucleotide payloads to muscle and CNS tissues

This study develops anti-TfR1 NANOBODY(R) molecules that deliver siRNA and ASO payloads to muscle and CNS tissues, achieving significant mRNA knockdown.

A Single Lipid Nanoparticle Formulation Enables Delivery of Diverse RNA Therapeutics to Human Muscle Models of Duchenne Muscular Dystrophy

A TLS11a-decorated ionizable lipid nanoparticle platform and a multilevel-validated CRISPR LDLR-knockout HepG2 model for hepatocyte-preferential mRNA delivery

The paper develops an LDLR-independent LNP platform for hepatocyte-targeted mRNA delivery and validates an LDLR-knockout HepG2 model for studying LDLR biology.

Establishing a genetic part library for tunable double-stranded RNA circuit construction and RNA interference in Caenorhabditis elegans

This paper develops a genetic part library for constructing tunable dsRNA circuits in C. elegans to enable precise RNA interference.

Post-loading ribonucleic acid into lipid nanoparticle carriers

This paper introduces a post-loading method for mRNA into lipid nanoparticles to reduce cold storage requirements, achieving comparable delivery efficiency to conventional methods.

Resolving heterogeneity of targeted lipid nanoparticles through solution-based biophysical analyses

This study resolves heterogeneity in targeted lipid nanoparticles (tLNPs) using biophysical methods, showing that subpopulation structure, not bulk properties, determines targeted RNA delivery.

Combination siRNA delivery as a therapeutic strategy for ADPKD

This study demonstrates that dual-target siRNA delivery using CD-targeting micelles reduces cyst growth in ADPKD models by silencing TMEM16A and MCP-1.

An aptamer targeting TfR1 enhances ASO delivery to muscle tissue

This study evaluates an aptamer targeting TfR1 for enhancing ASO delivery to muscle tissue, showing >50% target gene knockdown in mice for 42 days.

DNA-Programmed Condensate-Membrane Wetting and Cellular Internalization

This study designs DNA condensates that control their interaction with cell membranes, showing that internalization depends on a balance between adhesion and fluidity, not just affinity.

Lipid nanoparticle co-delivery of mRNA and a small molecule drug for oral cancer chemoimmunotherapy

This paper develops a lipid nanoparticle co-delivering mRNA and a small molecule drug to treat oral cancer by enhancing chemotherapy and reshaping the tumor microenvironment.

Structural dynamics between Argonaute-2 and CK1α promote target RNA release in microRNA-mediated silencing

The paper reveals how structural dynamics between Ago2 and CK1α facilitate target RNA release during miRNA-mediated silencing through phosphorylation of the EI domain.

Conserved core RNAi machinery in trematode-vectoring snails indicates gene silencing potential in the absence of classical systemic and amplification effectors

The paper identifies conserved RNAi effector genes in trematode-vectoring snails, suggesting potential for RNAi-based disease control despite lacking classical systemic and amplification components.

CPP2Vec: a Representation Learning Approach for Cell-Penetrating Peptides Prediction

The paper introduces CPP2Vec, a Word2Vec-based method for predicting cell-penetrating peptides, and compares it with pre-trained LLM-based models, showing strong predictive performance.

Peptide additives reprogram the lipid nanoparticle corona and enhance gene delivery in a serum-free environment for lung epithelium

This study develops peptide-lipid nanoparticles (hpLNPs) for pulmonary DNA delivery, showing enhanced transgene expression and demonstrating the importance of serum interactions for in vivo efficacy.

Utilization of Cell-penetrating Peptide Adaptors to Enhance Delivery of Variably Charged Protein Cargos

This study evaluates how different cell-penetrating peptide adaptors affect the internalization of variably charged protein cargos, revealing that adaptor charge and design significantly influence delivery efficiency.

Pulmonary mRNA-LNP Vaccines for Rapid and Durable Protection Against Bacterial Infection

This paper develops a pulmonary mRNA-LNP vaccine that provides rapid and durable protection against bacterial lung infections by integrating innate and adaptive immune responses.

Physiologically Based Pharmacokinetic Modeling of mRNA-Encoded Therapeutics: A Multiscale Framework for LNP and Antibody Trafficking in Mice

The paper develops a multiscale pharmacokinetic model integrating mRNA trafficking and antibody disposition in mice, validated with experimental data to predict biodistribution and optimize dosing.

Accurately modelling RNase H-mediated antisense oligonucleotide efficacy

The paper develops ASO Atlas, a database of RNase H-mediated ASO sequences and their efficacy, and trains OligoAI, a deep learning model to predict ASO efficacy based on sequence and chemical features, reducing screening effort by 5.72-fold.

Fucoidan-Coated Layer-by-layer Lipid Nanoparticles for the Generation of CAR-Macrophages

This study develops fucoidan-coated lipid nanoparticles (Fuc-LNPs) for improved RNA delivery to macrophages, demonstrating enhanced targeting and transfection efficiency compared to PEGylated controls.

Cell Penetrating Thyclotides Facilitate Efficient Delivery of Bioactive Peptides into Cells

This study demonstrates that cell penetrating thyclotides enhance the cellular uptake and endosomal escape of bioactive peptides, improving their therapeutic potential.

Intracellular Delivery of Peptides and Proteins with an Engineered Membrane Translocation Domain

This paper develops an engineered membrane translocation domain (MTD4) that enables efficient intracellular delivery of peptides and proteins, demonstrating its effectiveness in vitro and in vivo.

Lipid Nanoparticles Enable mRNA Delivery to Diverse Cell Types of the Inner Retina

This study shows that lipid nanoparticles can deliver mRNA to various inner retinal cell types, with higher efficiency in degenerate retinas and when the inner limiting membrane is removed.

Revealing a Correlation between Structure and in vitro Activity of mRNA Lipid Nanoparticles

This study investigates the structure-activity relationship of mRNA-LNPs, finding that a more ordered internal structure correlates with higher in vitro activity.

RNA post hoc loading into empty lipid nanoparticles occurs on millisecond timescales during turbulent mixing

The paper investigates RNA post hoc loading into empty lipid nanoparticles using turbulent mixing and finds it occurs within 12 ms under optimal conditions.

Intracellular delivery of full-length antibodies via organ targeted lipid nanoparticles

This paper develops lipid nanoparticles for intracellular antibody delivery, showing efficacy in inhibiting cytosolic targets in cancer and disease models.

Bottlebrush Polymer Conjugates for Enhanced Antisense Oligonucleotide Therapy in Myotonic Dystrophy Type 1

This paper demonstrates that bottlebrush polymer conjugates enhance antisense oligonucleotide therapy for DM1, improving muscle distribution and splicing correction in a mouse model.

Efficient delivery of mRNA-LNPs in primary and secondary liver cancer

This study shows that mRNA-LNPs can efficiently deliver mRNA to hepatocytes in healthy and diseased livers, including tumors, suggesting potential for systemic mRNA therapy in liver cancer.

FALCON: Closed-Loop Multi-Objective Optimization of Lipid Nanoparticles for Cell-Selective mRNA Delivery

FALCON optimizes lipid nanoparticles for cell-selective mRNA delivery, improving transfection efficiency and selectivity in vivo.