Virus-based gene therapy research

Postnatal gene restoration in succinic semialdehyde dehydrogenase deficiency (SSADHD) reveals phenotype reversibility

This study shows that restoring the ALDH5A1 gene in a mouse model of SSADHD reverses hyperactivity and reduces GHB levels, improving survival.

Preclinical validation of AAV9-TECPR2 gene therapy in a novel knock-in model of TECPR2-related disorder

This study develops a TECPR2 knock-in mouse model and shows that AAV9-mediated gene therapy improves mechanosensory function, gait, and startle responses in neonatal mice with TECPR2 deficiency.

LRP6-Guided Engineering of AAV9 Variants with Enhanced Blood-Brain Barrier Penetration and Reduced Liver Tropism in Non-Human Primates

This study engineers AAV9 variants guided by LRP6 to enhance BBB penetration and reduce liver tropism in non-human primates.

In vivo-directed evolution identifies AAV-WM04 as a next-generation vector for potent and durable hearing restoration in DFNB9

This study identifies AAV-WM04 as a highly efficient and safe gene delivery vector for targeting inner hair cells in the cochlea, showing effectiveness in mice and non-human primates for treating hereditary hearing loss.

A genome-wide CRISPR-Cas9 screen identifies TGN46 as a host determinant for H-1PV susceptibility in pancreatic adenocarcinoma.

The paper identifies TGN46 as a host factor critical for H-1PV infection in pancreatic cancer cells through a CRISPR-Cas9 screen and functional analyses.

Spatial Transcriptomics and Single-Nucleus RNA Sequencing Reveal rAAV2- and rAAV9-Specific Transduction Signatures in the Mouse Liver

This study uses spatial transcriptomics and single-nucleus RNA sequencing to analyze rAAV2 and rAAV9 vector effects in mouse livers, revealing sex-specific transcriptomic changes and novel transgene co-expression factors.

The adeno-associated virus Rep proteins target PP4:SMEK1 by preventing substrate-recruitment

This study identifies PP4:SMEK1 as a host restriction factor suppressed by AAV Rep proteins through substrate-recruitment interference, enhancing rAAV vector potency.

AAV-Mediated Dual-Gene Therapy Restores Metabolic Function in Mice with Propionic Acidemi

This study demonstrates that dual-gene AAV therapy restores metabolic function and shows long-term safety in a mouse model of propionic acidemia.

Synthetic Genome Shuffling of Poxviruses through Yeast for Next-Generation Oncolytic Platforms

The paper describes a method using yeast-based genome shuffling to generate chimeric poxviruses with enhanced oncolytic activity and immune stimulation.

A Multispecies, Modality-Agnostic Scalable In Vivo Mosaic Screening Platform for Therapeutic Target Discovery

The paper presents an in vivo screening platform for validating therapeutic targets across species and modalities, identifying functional targets in fibrosis and osteoarthritis models.

Nanoneedle-Enabled Quantification of rAAV9 Capsid and Genome Integrity Reveals a Truncation Hotspot Locus in a 4.5 kb Transgene

The paper uses nanoneedle technology to quantify AAV9 capsid and genome integrity, identifying a truncation hotspot and characterizing particle heterogeneity.

Replication competent adenoviral platform for in situ production of immunotherapeutic RNA aptamers targeting 4 1BB

This paper develops a replication-competent adenovirus platform for in situ production of RNA aptamers targeting 4-1BB, showing antitumor activity comparable to a 4-1BBL-expressing adenovirus.

A novel Gorilla-derived oncolytic Adenovirus with natural selective replication in cancer cells

This paper develops a novel gorilla-derived oncolytic adenovirus, GRAd32Fk25, which selectively replicates in tumor cells and expresses a therapeutic antibody, showing potential as an improved virotherapy compared to HAd5.

Synthetic Serum Markers Enable Noninvasive Monitoring of Gene Expression in Primate Brains

This study introduces RMAs, synthetic serum markers that enable noninvasive monitoring of gene expression in primate brains via blood tests over three months.

A Cross-Species Enhancer-AAV Toolkit for Cell Type-Specific Targeting Across the Basal Ganglia

The paper develops a cross-species enhancer-AAV toolkit for targeting specific cell types in the basal ganglia across species, validated in mouse and macaque.

The interaction between virus-bound KLF4 and host-bound PARP1 directs the localization of Adeno-Associated Virus Type 2 (wtAAV2) to cellular sites of DNA damage

This paper identifies a mechanism by which wtAAV2 localizes to DNA damage sites via KLF4 and PARP1 interactions, showing that enhancing KLF4 binding improves rAAV vector performance.

Adeno-Associated Virus-Induced Neurotoxicity is Prevented by CpG Depletion

This study shows that reducing CpG motifs in AAV genomes prevents neurotoxicity in mice and provides a tool to design CpG-depleted AAV vectors.

Development of a Serum-Free Producer Cell Line Generation Process for Scalable and Efficient rAAV Production for gene therapy applications

This study develops a serum-free process for generating producer cell lines for scalable and efficient rAAV production, achieving productivity and quality comparable to serum-based methods.

Prevention of Transgene Silencing During Human PluripotentStem Cell Differentiation

The paper identifies strategies to prevent transgene silencing during human pluripotent stem cell differentiation and introduces a robust vector construct.

Dual AAV amelioration of Lama2-null muscular dystrophy and neuropathy

This paper uses AAV9 to deliver genes for LNNdΔG2 and miniagrin in Lama2-null mice, improving survival, mobility, and nerve histology.

PRISM-Seq: An Ultra-sensitive Sequencing Approach For Mapping Lentiviral Integration Sites

PRISM-seq is an ultra-sensitive method for detecting lentiviral integration sites, validated at the single-molecule level with a quality control framework to reduce artifacts.

Non-clinical safety of GRAd vector-based COVID-19 and HIV vaccines supports a platform regulatory approach

This study evaluates the non-clinical safety of two GRAd vector-based vaccines for COVID-19 and HIV, showing consistent safety profiles and supporting a regulatory platform approach.

Dual AAV gene therapy using laminin-linking proteins ameliorates muscle and nerve defects in LAMA2-related muscular dystrophy

This paper describes a dual AAV gene therapy approach using linker proteins to restore basement membrane function in LAMA2 MD, showing significant improvements in muscle and nerve defects.

Protein-only centromeric chromatin assembly streamlines human artificial chromosome formation

This paper describes the creation of a 2 Mb human artificial chromosome (HAC) using a protein-only centromere seeding approach that bypasses genetic engineering of target cells.

Identification a Compact Promoter using a New Promoter Selection Strategy and Engineering Hybrid Pol II/III Enable Efficient Genome Editing in Human Retinal Ganglion Cells

The paper identifies a compact Pol II promoter and hybrid Pol II/III promoters to enable efficient single-AAV delivery of SpCas9 for genome editing in human retinal ganglion cells.

Overcoming lentiviral delivery limitations in hard-to-transduce suspension cells for genome-wide CRISPR screening

This study improves lentiviral transduction efficiency in suspension cells for CRISPR screening by optimizing protocols and analyzing integration patterns.

Efficient delivery of gene editors using intein-engineered virus-like particles

This paper develops intein-engineered virus-like particles for efficient gene editing delivery, achieving robust gene editing in multiple cell types and organs.

Systemic AAV delivery of a calcium indicator in marmosets: functional validation in visual area MT

This study demonstrates that systemic AAV delivery enables widespread calcium indicator expression in marmosets, allowing functional optical imaging of visual area MT at multiple scales.

Barrier Function of the Extracellular Matrix in AAV Gene Therapy

This study investigates how the extracellular matrix affects AAV gene therapy by comparing diffusion and transduction efficiency across different AAV serotypes and ECM models.

Long-Term Expression and Safety of AAV1-Mediated PI3Kδ Overexpression in the Adult Rat Cortex

This study shows that long-term PI3Kδ overexpression in adult rat cortex using AAV1 is safe and well-tolerated, with no adverse effects observed over one year.