Virus-based gene therapy research

EvoPRAISE: computationally guided directed evolution for rational AAV capsid engineering

This paper develops EvoPRAISE, a framework combining structure-based affinity prediction and directed evolution to design AAV capsids targeting the BBB in non-model species and humans.

Identification of genome safe harbor loci for human gene therapy based on evolutionary biology and comparative genomics

The paper identifies genome safe harbor loci for gene therapy using evolutionary biology and comparative genomics, finding nine loci with sustained transgene expression in human hematopoietic stem cells.

AAVs Targeting Human Carbonic Anhydrase IV Enhance Gene Delivery to the Brain

This study engineers AAVs targeting human carbonic anhydrase IV to enhance brain gene delivery, finding that optimized variants achieve 100-fold greater transduction than AAV9.

AAV-mediated CSNK2B gene replacement rescues ASD-relevant phenotypes and establishes EEG biomarkers for translation in Csnk2b haploinsufficient mice

This study shows that AAV-mediated CSNK2B gene replacement in Csnk2b haploinsufficient mice rescues ASD-like phenotypes and restores EEG biomarkers, supporting its use as a translational readout for gene therapy.

Longitudinal assessment of DREADD expression and efficacy in the monkey brain

This study longitudinally assesses DREADD expression and efficacy in macaque monkeys using PET imaging and functional studies, showing peak expression at 60 days and sustained effects for two years.

Exacerbation of a Subset of Behavioral Phenotypes by Early Treatment with AAV FOXG1 Gene Replacement Therapy in a Mouse Model of FOXG1 Syndrome

This study shows that early AAV FOXG1 gene therapy in female mice worsens motor behaviors, while it benefits males, highlighting gender-specific risks in potential human treatments.

Adenovirus maturation establishes the transcription competent packaging of its genome

This study identifies genomic regions that become decompacted during adenovirus maturation, revealing how DNA sequence features guide genome organization for transcription.

OASIS: in vivo AAV-mediated transduction and genome editing of adult oligodendrocytes

OASIS enables precise, customizable genome editing and subcellular visualization of adult oligodendrocytes using AAV-mediated CRISPR and biotinylation.

Transcriptional changes in non-human primate tissues after intrathecal delivery of serotype 9 adeno-associated viral vector: insights into organ toxicities

This study examines transcriptional changes in non-human primate tissues after AAV9 vector delivery, finding significant immune-related gene upregulation in liver and DRG.

AAV Kills Dividing Cells by Depleting PARP1 and Other DNA Damage Response Proteins

This study identifies that rAAV toxicity in dividing cells results from depletion of PARP1 and other DNA damage response proteins, leading to replication stress and cell death.

Oncolytic Maraba virus MG1 mediates direct and natural killer cell-dependent lysis of Ewing sarcoma

This study shows that the oncolytic Maraba virus MG1 can directly kill Ewing sarcoma cells and enhance NK cell-mediated cytotoxicity against them.

AAV11 mediates efficient retrograde trans-neuronal transduction of astrocytes

This paper demonstrates that AAV11 enables retrograde trans-neuronal transduction of astrocytes, providing a tool to study astrocyte-neuron connectivity networks.

Aviadenovirus structure: a highly thermostable capsid in the absence of stabilizing proteins

This paper reports the high-resolution structure of fowl adenovirus serotype 4, revealing unique structural features that contribute to its thermostability despite lacking stabilizing proteins.

High-Resolution Characterization of rAAV Genomes for Vector Quality Using Long-Read Sequencing

This paper uses long-read sequencing to characterize rAAV genomes and impurities, enabling better quality control in gene therapy production.

Systemic tumor-targeting gene drive vectors proactively eliminate drug resistance in solid tumors

This paper develops tumor-targeting gene drive vectors that eliminate drug resistance in solid tumors through systemic delivery, showing durable tumor burden reduction with minimal toxicity.

Automation of high-throughput arrayed lentivirus production and titration

This paper develops an automated workflow for high-throughput lentivirus production and titration, achieving high reproducibility and efficiency in generating CRISPR libraries.

Disabling a key viral innate immunity antagonist converts measles vaccine into RIG-I-driven cancer immunotherapy

This paper modifies a measles vaccine by removing a viral protein to create a cancer immunotherapy that activates the immune system via RIG-I signaling, leading to tumor regression in multiple models.

Optimization of the VSV G backbone for amino terminal fusion with nanobodies allowing its retargeting to receptors of therapeutic interest.

The paper identifies mutations in the VSV G glycoprotein that improve its functionality when fused with nanobodies, enabling specific retargeting to therapeutic receptors.

The structure of the Human Adenovirus 7 virus-like particles reveals that pentons and core-genome promote hexon-pIIIa interactions during capsid maturation

This paper reports the cryo-EM structure of human adenovirus 7 virus-like particles, revealing interactions critical for capsid maturation and stability.

Identification of a novel structural motif and overexpression of key transcripts elucidated in Adenovirus 10

The paper identifies a novel structural motif in the HAdV-D10 capsid and reports overexpression of a key transcript, providing insights for vector development.

A single amino acid variant in the variable region I of AAV capsid confers liver detargeting

The paper identifies an amino acid variant in AAV capsid VR-1 that reduces liver targeting, suggesting its potential for minimizing liver toxicity in gene therapy.

Spatial and longitudinal tracking of enhancer-AAV vectors that target transgene expression to injured mouse myocardium

The paper tracks enhancer-AAV vector expression in injured mouse myocardium using bioluminescent imaging to evaluate spatial and temporal dynamics and identify improved capsids for targeted transgene delivery.

Epithelial competition determines gene therapy potential to suppress Fanconi Anemia oral cancer risk

This paper uses a computational model to show that gene-corrected cells must have strong proliferative advantages to spread in the oral epithelium and that delivering correction to many cells reduces stochastic loss.

Alphavirus replicons encoding IFNγ enhance cancer virotherapy by overcoming macrophage-mediated suppression

This study shows that alphavirus replicons encoding IFNγ enhance cancer virotherapy by overcoming macrophage-mediated suppression through T-cell activation and macrophage reprogramming.

The limited effects of AAV2 vectors on host chromatin accessibility and nuclear architecture are consistent with a favorable safety profile

Design, development, and evaluation of gene therapeutics specific to KSHV-associated diseases

This paper develops a gene therapy vector targeting KSHV-infected cells using AAV8-TR2-OriP-TK, which, when combined with ganciclovir, effectively eradicates KSHV-associated cancers in xenograft models.

Fluctuations in AAV genome quantification via digital PCR affected by heat-based virion lysis

This study shows that shorter amplicons in dPCR lead to higher AAV genome copy numbers, indicating heat-induced fragmentation affects quantification.

Genome-replicating HC-AdV, a novel high-capacity adenoviral vector class featuring enhanced in situ payload expression

This paper develops a genome-replicating high-capacity adenoviral vector that enhances transgene expression without causing host cell death.

Modeling integration site data for safety assessment with MELISSA

MELISSA assesses insertional mutagenesis risk by analyzing integration site data, identifying over- and under-targeted genes and their impact on clone fitness.

Dual S100A1 and ARC gene therapy as a treatment for DMD cardiomyopathy

This paper investigates dual S100A1 and ARC gene therapy for DMD cardiomyopathy, showing improved cardiac function and survival in mouse models and safety in canine models.