Virus-based gene therapy research

Engineering multiple levels of specificity in an RNA viral vector

The paper demonstrates a viral delivery system with multiple control levels for targeted therapy using engineered components in a rabies virus model.

TRACE-Seq Reveals Clonal Reconstitution Dynamics of Gene Targeted Human Hematopoietic Stem Cells

The paper introduces TRACE-Seq, a method to track clonal reconstitution of gene-targeted human hematopoietic stem cells using barcoded AAV6 donor templates in immunodeficient mice.

Methods Matter -- Standard Production Platforms For Recombinant AAV Produce Chemically And Functionally Distinct Vectors

This study compares rAAV production methods using different host cells, finding chemically and functionally distinct vectors with differences in PTMs, methylation, and potency.

Intra-articular AAV-PHP.S mediated chemogenetic targeting of knee-innervating dorsal root ganglion neurons alleviates inflammatory pain in mice.

This study uses AAV-PHP.S to deliver chemogenetic receptors to knee-innervating DRG neurons, showing that inhibitory DREADDs reduce inflammation-induced pain in mice.

Quantification of Adeno-Associated Virus with Safe Nucleic Acid Dyes

The paper describes a method using safe nucleic acid dyes to quickly and reliably quantify Adeno-Associated Virus (AAV) titers.

Intra-striatal AAV2.retro administration leads to extensive retrograde transport in the rhesus macaque brain: implications for disease modeling and therapeutic development

This study shows AAV2.retro efficiently transports gene cargo retrogradely in rhesus macaque brains, enabling widespread transduction of brain circuits relevant to Huntington's disease.

Enhancer viruses and a transgenic platform for combinatorial cell subclass-specific labeling

The paper develops enhancer viruses and a transgenic mouse line to enable combinatorial labeling of specific neuronal subclasses in the mouse cortex and human slices.

SMALL ALPHAHERPESVIRUS LATENCY-ASSOCIATED PROMOTERS DRIVE EFFICIENT AND LONG-TERM TRANSGENE EXPRESSION IN THE CENTRAL NERVOUS SYSTEM

The paper identifies small herpesvirus latency-associated promoters that enable long-term, pan-neuronal transgene expression in the CNS using AAV vectors.

In vivo directed evolution of AAV in the primate retina

This study uses directed evolution to create AAV vectors with enhanced gene delivery to the outer retina in primates.

Anterograde Trans-Synaptic AAV Strategies for Probing Neural Circuitry

This study demonstrates that AAV1 preferentially spreads transsynaptically through glutamatergic and GABAergic synapses, enabling the labeling of neurons based on their input sources and molecular identities.

Gene replacement therapy provides benefit in an adult mouse model of Leigh syndrome

This paper demonstrates that gene replacement therapy using AAV-PHP.B vector improves survival and corrects metabolic and behavioral deficits in a mouse model of Leigh syndrome.

Regulated control of gene therapies with a drug induced switch

This paper introduces a drug-inducible switch system (Xon) for precise control of gene therapies, enabling gene silencing or replacement with oral small molecule inducers that are safe and bioavailable.

Monosynaptic tracing success depends critically on helper virus concentrations

The paper shows that helper virus concentrations significantly affect transsynaptic tracing efficiency and nonspecific labeling in monosynaptic tracing experiments.

Generation of light-producing somatic-transgenic mice using adeno-associated virus vectors

The paper develops a method using adeno-associated virus vectors to generate somatic-transgenic mice for non-invasive monitoring of signaling pathways in disease models.

Functional enhancer elements drive subclass-selective expression from mouse to primate neocortex

The paper identifies enhancer elements that drive subclass-specific gene expression in neocortex across mouse, primate, and human species using comparative epigenetics and AAV-based functional assays.

Barcoded Rational AAV Vector Evolution enables systematic in vivo mapping of peptide binding motifs

The paper introduces BRAVE, a method for rational AAV vector evolution that maps peptide binding motifs in vivo using barcoding and clustering.

Adeno-Associated Virus Technologies and Methods for Targeted Neuronal Manipulation

The paper discusses strategies for targeted neuronal manipulation using adeno-associated virus (AAV) and other technologies, emphasizing best practices and future directions.

Delivering genes across the blood-brain barrier: LY6A, a novel cellular receptor for AAV-PHP.B capsids

The paper identifies LY6A as a novel receptor for AAV-PHP.B vectors, enabling efficient gene delivery across the blood-brain barrier in mice.

Using a bar-coded AAV capsid library to select for novel clinically relevant gene therapy vectors

The paper develops a barcoded AAV capsid library to identify novel gene therapy vectors with improved transduction efficiency in human islets and hepatocytes.

Homologous recombination-based genome editing by clade F AAVs is inefficient in the absence of a targeted DNA break

The paper evaluates clade F AAVs for homologous recombination-based genome editing without DSBs, finding no detectable editing without ZFNs.

Identification of cerebellar afferent projections in a nonhuman primate using CAV-2 vectors

This study tests the use of CAV-2 vectors in a nonhuman primate cerebellum to identify afferent projections and assess retrograde transport.

Two-Step Small Scale Purification of Recombinant Adeno-Associated Viruses

The paper describes a two-step purification method for recombinant AAVs from small starting material, achieving comparable titer and purity to commercial samples.

Targeting neuronal and glial cell types with synthetic promoter AAVs in mice, non-human primates, and humans

The paper develops synthetic promoter AAVs for cell-type-specific gene delivery in mice, non-human primates, and humans, showing 11% of AAVs target neuronal and glial cell types in multiple species.

Asymmetrical cleavages of Sleeping Beauty transposons generate multiple excised transposon fragments during transposition

The paper investigates SB transposon excision and integration, finding asymmetrical cleavage generates multiple fragments and only some re-integrate, impacting transposition efficiency.

Generation of viral vectors specific to neuronal subtypes of targeted brain regions by Enhancer-Driven Gene Expression (EDGE)

The paper develops viral vectors with brain region-specific gene expression using enhancer-driven gene expression (EDGE) to enable circuit-specific manipulations in any species.

Aberrant Clonal Hematopoiesis Following Lentiviral Transduction of HSPC in a Rhesus Macaque

This paper reports a case of clonal hematopoiesis in a rhesus macaque following lentiviral transduction of HSPC with a strong retroviral promoter, leading to gene overexpression and aberrant splicing.

Transverse sinus injections: A novel method for whole-brain vector-driven gene delivery

This paper introduces a method for efficient whole-brain gene delivery in neonatal rats and mice using transverse sinus injections of AAV9.

Epilepsy gene therapy using non-integrating lentiviral delivery of an engineered potassium channel gene

This paper develops a non-integrating lentiviral gene therapy for refractory focal epilepsy, showing reduced seizure frequency in a rat model.

retroLEAP: rAAV-based retrograde trans-synaptic labeling, expression and perturbation

RetroLEAP enables retrograde trans-synaptic labeling, expression, and perturbation of neurons using a GFP-dependent recombinase system.

AAV-mediated progranulin delivery to a mouse model of progranulin deficiency causes T cell-mediated hippocampal degeneration

This study shows that AAV-mediated GRN overexpression in mice causes hippocampal degeneration and T cell infiltration, raising safety concerns for GRN-based CNS gene therapies.