Virus-based gene therapy research

Single-AAV Delivery of the SpCas9 Nickase Improves CAG/CTG Repeat contraction in a mouse model of Huntington's disease

This study demonstrates that a single-AAV vector delivering the SpCas9 nickase and sgRNA achieves greater CAG/CTG repeat contraction in a Huntington's disease mouse model compared to a dual-vector system.

E. coli-produced nanobody fusions as a pan-serotype platform for AAV purification, quantification, and detection

This paper develops nanobody AAVX fusion proteins for AAV purification, quantification, and detection across multiple methods.

End-To-End, Fully Automated Manufacturing of Hematopoietic Stem and Progenitor Cell Therapy Via CCR5-Targeted Integration

This paper demonstrates an automated, high-throughput platform for manufacturing gene-edited hematopoietic stem and progenitor cells (geHSPCs) with preserved function and in vivo engraftment capacity.

Implementation and Evaluation of Marker Rescue and qPCR Assays for Detection of Replication-Competent Retrovirus in Gene Therapy Products

This study evaluates marker rescue and qPCR assays for detecting replication-competent retrovirus in gene therapy products, showing improved sensitivity with amplification steps.

Oncolytic Newcastle disease virus promotes tumor cell apoptosis through SUMO-1-dependent PRKN-mediated degradation of c-Myc

Megalin-mediated deterministic pseudotransduction in proximal tubules fundamentally challenges current understanding of AAV kidney transduction

The paper shows that AAV-mediated gene delivery to proximal tubules is not direct but relies on megalin-mediated uptake of reporter proteins from other organs, challenging current understanding.

Adeno-associated virus serotype tropism and transduction in murine dorsal root ganglia following direct injection.

This study evaluates AAV serotype transduction efficiency in murine dorsal root ganglia, finding that AAV8, AAV9, and PHP.S show comparable efficiency but distinct neuronal volume distributions.

Programmable Surface Receptor-Mediated Cell Targeting with Designer Antibody-Routed Nanoparticles (DARTs)

The paper introduces DARTs, a platform for programmable cell targeting using antibody-conjugated nanoparticles, identifying new surface antigens for gene editing in neural cells.

Cryo-EM Reveals VP1/VP2 N-Terminal Conformations in Adeno-Associated Virus 2 Capsids.

The paper uses cryo-EM to reveal distinct N-terminal conformations of VP1/VP2 in AAV2 capsids with different VP stoichiometries, linking them to structural heterogeneity.

A modular lentiviral system for multiplexed gene perturbation and functional analysis suggests interdependence of hormone receptors in breast cancer growth in vivo

The paper introduces a modular lentiviral system for multiplexed gene perturbation and functional analysis, showing that ER+ breast cancer cells rely on AR, ER, and PR for in vivo growth.

Biomarker-driven and gene-enhanced viral therapy for malignant peripheral nerve sheath tumor

This study develops a gene-enhanced HSV therapy for MPNST by exploiting PRC2 loss and tumor-regulated ICP34.5 expression to improve viral efficacy.

Long terminal repeats influence deletion propensity and genome instability in proviruses across major retroviruses

This study shows that retroviral LTRs increase the likelihood of large internal deletions in proviruses, with HIV-1 and HTLV-1 LTRs showing higher deletion rates than HIV-2.

Intracellular accumulation of AAV6 genomes governs microglia reactivity and the inflammatory response in retinal gene therapy

This study shows that intracellular accumulation of AAV6 genomes in microglia drives reactivity and inflammation in retinal gene therapy.

Minimally Invasive in Situ Perfusion Method for Targeted AAV Delivery in Native Kidney: Proof of Concept in Pigs

This paper develops a minimally invasive method for targeted AAV delivery to the native kidney in pigs, reducing liver off-target effects and enabling in-situ perfusion.

A minimally modified AAV9 variant (AAV9fyhr) for enhanced CNS gene delivery by intra-CSF administration.

This paper describes a novel AAV9 variant, AAV9fyhr, that improves CNS gene delivery while minimizing peripheral tissue tropism through targeted amino acid modifications.

Streamlined Production of Recombinant Adeno-Associated Viruses Using Gateway Cloning Technology for Neural Circuit All-Optical Interrogation

The paper introduces a Gateway-based cloning platform for efficient construction of rAAV vectors optimized for neuroscience applications, enabling precise optical interrogation of neural circuits with tools like ULoVE.

Machine learning-assisted directed evolution yields dramatic improvement on novel AAV engineering task

This study shows ML-assisted directed evolution improves AAV capsid manufacturing efficiency 41-fold compared to directed evolution alone.

A novel adenovirus 19K/IX protein enhances infection by attenuating proteasomal degradation of tyrosine-ubiquitinated capsid protein IX

This study identifies the 19K/IX protein as a regulator of HAdV-C5 infection by stabilizing the capsid protein IX through attenuation of proteasomal degradation.

Juvenile AAV-Mediated MEF2C Gene Replacement Ameliorates Selected Phenotypes in Mef2c-Haploinsufficient Mice

This study shows that juvenile AAV-mediated MEF2C gene replacement can improve specific phenotypes in Mef2c-haploinsufficient mice.

AAV-mediated TBR1 replacement ameliorates behavioral and electrophysiological abnormalities in Tbr1-haploinsufficient mice

This study shows that AAV-mediated TBR1 replacement in Tbr1-haploinsufficient mice improves some behavioral and electrophysiological outcomes but not all abnormalities.

BI-TfR1 CapX rapidly transits the blood-brain barrier for efficient, low-dose gene delivery throughout the CNS

The paper describes BI-TfR1 CapX, a gene delivery vector that efficiently crosses the blood-brain barrier, transduces CNS neurons and astrocytes, and reduces Prnp mRNA with low doses.

Plasmid architecture determines the stability of inverted terminal repeats in adeno-associated virus vectors

The paper identifies position-dependent ITR instability in AAV plasmids and develops a stable rAAV vector with full-length native ITRs.

Systemic tumor-cell reprogramming converts solid tumors into in situ biofactories for immunotherapy

LENTRA reprograms tumor cells to produce therapeutic molecules, inducing antitumor immunity and durable immune memory in mouse models and patient-derived explants.

KLHL40 gene replacement therapy in severe nemaline myopathy improves survival and skeletal muscle function in a preclinical mouse model

AAV-mediated SIL1 gene therapy prevents cerebellar degeneration and ataxia in a mouse model of Marinesco-Sjögren syndrome

AAV-mediated SIL1 gene therapy prevents cerebellar degeneration and ataxia in a mouse model of Marinesco-Sjögren syndrome by preserving Purkinje cells and reducing ER stress.

Host Endoplasmic Reticulum Stress and Interferon Responses Contribute to AAV-Induced Ocular Toxicity

In neonatal mice, AAV-driven GFP overexpression in RPE shows ER stress signatures and partly CHOP-dependent RPE damage, while IFNAR loss partly spares photoreceptors.

Nanobody-Functionalized AAV achieves Promoter-independent Neuronal Targeting in the CNS

This paper develops AAV-m5, a nanobody-functionalized AAV vector that targets neurons via mGluR5, achieving efficient and specific transduction in the CNS without relying on promoters.

Zika virus oncolytic signaling reverts immunosuppressive and angiogenic glioblastoma microenvironment in vitro and in vivo

This study shows that Zika virus reprograms the glioblastoma tumor microenvironment to be anti-tumoral by inducing type III interferon signaling, which can be mimicked by exogenous treatment.

In vivo HSPC gene therapy of hemoglobinopathies without drug selection of corrected cells

This study demonstrates in vivo gene therapy for hemoglobinopathies using EPOR editing to enhance the expansion of gene-corrected erythroid cells without drug selection.

Integrated Continuous Biomanufacturing of Recombinant Adeno-Associated Virus

This paper introduces a continuous biomanufacturing platform for rAAV that improves yield and reduces process complexity compared to conventional batch methods.