Virus-based gene therapy research

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.

Development of a recombinant adeno-associated virus vector for human T lymphocyte- and natural killer cell-targeted gene therapy

This paper develops a CD7-targeted rAAV vector for efficient gene delivery to human T and NK cells, showing reduced off-target effects and improved transgene expression through genome optimization.

Oncolytic virus-antibody combinations enhance immune-mediated killing of osteosarcoma

This study shows that combining oncolytic viruses with antibodies enhances immune-mediated killing of osteosarcoma by overcoming immunosuppression.

RNA trans-splicing treatment for Duchenne muscular dystrophy

The paper develops a multi-vector RNA End Joining system for Duchenne muscular dystrophy that enables efficient expression of large therapeutic proteins with minimal off-target effects.

P5 promoter-mediated incorporation explains REP/CAP manufacturing contaminants in patient liver after rAAV gene therapy

The paper identifies a mechanism by which REP/CAP contaminants arise in rAAV gene therapy through P5 promoter-mediated incorporation during manufacturing.

Explainable Machine Learning and Epigenomic Profiling Decipher the Topological Determinants of Lentiviral Integration and Longitudinal Persistence in SCID-X1 Gene Therapy

The paper uses machine learning and epigenomic profiling to identify determinants of lentiviral integration and persistence in SCID-X1 gene therapy, finding significant depletion of persistent clones near proto-oncogenes.

AAV delivered lysosome-targeting chimeras mediate sustained antibody depletion in vivo

This paper develops GELYTACs, lysosome-targeting chimeras that deplete IgG in vivo via AAV delivery, showing sustained antibody depletion in mice.

AAV-DJ Enables Targeted Gene Modulation in Human Ovarian Cells

This study demonstrates that AAV-DJ efficiently and safely transduces human ovarian cells, enabling targeted gene modulation with significant knockdown of AMHR2 and TGF{beta}1.

Ex vivo human tumor slices more accurately predict patient responses to an oncolytic virus than in vivo mouse models

This study shows that human tumor slices better predict patient responses to an oncolytic virus than mouse models, highlighting indication-specific efficacy.

Adeno-Associated Virus Mediated Expression of Bcl-xL Attenuates Apoptosis in Fuchs Endothelial Corneal Dystrophy

This study evaluates AAV-mediated Bcl-xL expression in FECD to reduce apoptosis, finding significant protection in FECD CECs.

Combined Disruption of Multiple Cytokine Signaling Pathways Enables One-Step Anterograde Tracing with Vesicular Stomatitis Virus

This paper develops a VSVdG-based strategy for one-step anterograde tracing in neural circuits by disrupting cytokine signaling pathways and using AAV trans-complementation.

Development of the EASY-HSV (Efficient And Simple high-Yield Herpes Simplex virus Vector) system based on HSV-1 genome-maintaining HEK293 cells

The paper develops an EASY-HSV system using HSV-1 genome-maintaining HEK293 cells to simplify and increase the yield of HSV amplicon vector production.

Unravelling resistance mechanisms of oncolytic viruses in glioblastoma

This study identifies cellular processes driving oncolytic virus resistance in glioblastoma by analyzing resistant subclones from patient-derived cell lines.

Functional evaluation of a natural AAV capsid liver targeting motif in human hepatocytes

The paper evaluates a natural AAV capsid liver targeting motif in human hepatocytes using in vivo and in vitro models, showing its role in liver targeting and the impact of PEG on transduction.

Alpha Protein Kinase 3 Gene Therapy Restores Heart Function in Mouse and Human Models of Cardiomyopathy

This study shows that gene therapy with AAV-ALPK3 improves heart function in mouse and human models of cardiomyopathy caused by ALPK3 variants.

Divergent Entry, Convergent Trafficking in Defensin-Mediated Adenovirus Infection

This study compares intracellular trafficking of defensin-resistant and canonical adenovirus entry routes, finding they converge on common checkpoints and that defensin effects are determined at the cell surface.

TBC1D23-AAVR Interaction Drives Endosome-to-TGN Trafficking Required for rAAV Transduction

This paper identifies TBC1D23 as a host protein that binds AAVR and mediates endosome-to-TGN trafficking required for rAAV transduction.

Rab9 depletion enhances human adenovirus type 26 transduction efficiency through increased internalization and reduced late endosomal/lysosomal retention

This study shows that Rab9 depletion increases HAdV-D26 transduction efficiency by enhancing internalization and reducing late endosomal/lysosomal retention.

Tunable Expression of an AAV Payload Using ADAR-mediated RNA Editing

This paper demonstrates an ADAR-mediated gene switch to control AAV-delivered gene expression by rescuing a premature termination codon via RNA editing, achieving tunable and clinically relevant therapeutic protein levels.

Comparative analysis of microglia-targeted AAVs reveals capsid choice drives efficiency in vitro but has limited impact in vivo

The paper compares microglia-targeted AAVs, finding that capsid choice affects in vitro efficiency but not in vivo transduction when using specific promoters.

Protease-driven remodeling of stabilization networks during adenovirus assembly

The paper determines high-resolution structures of adenovirus particles at different proteolytic stages, revealing how protease-driven remodeling affects capsid stability and maturation.

A modified cyclosporine enhances lentivector transduction ex vivo and in vivo by degrading IFITM3

BG147 enhances lentivector transduction in HSPCs ex vivo and in mouse photoreceptors in vivo by degrading IFITM3.

AAV and lentiviral transduction in Duchenne muscular dystrophy cardiomyocytes activate cell stress responses

The paper shows that viral gene transfer in DMD cardiomyocytes activates stress responses and downregulates metabolic genes.

Structural Analysis of Recombinant AAV Vector Genomes at Single-Molecule Resolution

The paper develops a pipeline to classify AAV genome structures at single-molecule resolution using long-read sequencing, revealing structural heterogeneity and its contributing factors.

AAV2 Bypasses Direct Endosomal Escape by Using AAVR to Access the Trans-Golgi Network en Route to the Nucleus.

This study shows AAV2 bypasses endosomal escape by using AAVR to access the trans-Golgi network, challenging the model of direct endosomal escape.

Oncolytic Adenovirus Armed with cGAS Activates STING Pathway and Enhances Antitumor Immunity in Lung Cancer with Superior Combined Efficacy of PD-L1 Therapy

This study develops oncolytic adenoviruses expressing cGAS to activate the STING pathway and enhance antitumor immunity in lung cancer, showing improved efficacy when combined with PD-L1 therapy.

Polyvinylpyrrolidone enhances AAV transduction in vitro and shows preliminary utility for subretinal delivery

This study shows that polyvinylpyrrolidone (PVP) enhances AAV transduction in vitro and improves subretinal delivery in vivo.