Adeno-associated virus

The study established imaging conditions optimized for physiological temperature and oxygen because these conditions critically shape NO bioavailability.

We establish imaging conditions optimized for physiological temperature and oxygen, which critically shape NO bioavailability.

Both endogenous and exogenously applied NO dampen spontaneous Ca2+ spikes in primary hippocampal neurons.

Conversely, both endogenous and exogenously applied NO dampen spontaneous Ca2+ spikes

Robust Ca2+ elevation induced by high extracellular K+ or glutamate evokes robust NO signals in primary hippocampal neurons.

whereas robust Ca2+ elevation by high extracellular K+ (50 mM) or glutamate (30 μM) evokes robust NO signals

Under the optimized conditions, spontaneous Ca2+ spikes and network activity are largely insufficient to elicit detectable NO production in primary hippocampal neurons.

Under these conditions, spontaneous Ca2+ spikes and network activity are largely insufficient to elicit detectable NO production

MscS showed exceptional genomic compatibility with fewer off-target gene alterations than the MscL variants.

Optogenetics enables precise control of neural activity through light-sensitive opsins.

MscL-G22N produced weaker ultrasound responses than MscL-G22S despite having a lower mechanical threshold.

MscL-G22S showed strong ultrasound sensitivity in rat hippocampus, including amplified evoked potentials and reduced response latency under focused ultrasound.

NO signals evoked by robust Ca2+ elevation surpass responses to exogenous NO donors.

evokes robust NO signals that surpass responses to exogenous NO donors

Adeno-associated viruses and lentiviruses have shown promise for delivering targeted genetic interventions in epilepsy gene therapy.

viral vectors, such as adeno-associated viruses and lentiviruses, have shown promise in delivering targeted genetic interventions

The approved viral gene therapy products highlighted in the abstract rely on adeno-associated vectors and lentiviral vectors for delivery.

The review discusses AAVs, LNPs, lentivirus, and virus-like particles as emerging delivery vehicles for gene editing therapies targeting lipid metabolism in cardiovascular disease.

Emerging delivery vehicles (AAVs, LNPs, lentivirus, virus-like particles) and their translational implications are discussed.

Adeno-associated viruses are presented as a promising clinical delivery approach for opsins to target cells and can improve flexibility and accuracy of opsin delivery when combined with cell-specific promoters and serotype choice.

Advances in capsid engineering, tissue-specific promoters, and delivery strategies have enhanced podocyte targeting while minimizing off-target effects.

Improvements in viral-mediated gene transfer efficiency and clinical-scale manufacturing have helped propel the clinical adoption of gene therapy products.

Nearly 30 new viral gene therapy programs have been approved by the US FDA since the first AAV-based gene therapy approval in 2017.

Major challenges for epilepsy gene therapy include safe and efficient gene delivery, maintaining long-term therapeutic effects, and mitigating potential side effects.

However, significant challenges exist, including ensuring safe and efficient gene delivery, maintaining long-term therapeutic effects, and mitigating potential side effects.

The comparison between MscL-G22N and MscL-G22S suggests that ultrasound sensitivity depends on factors beyond nominal mechanical gating threshold.

The findings demonstrate bidirectional functional coupling between Ca2+ and NO signals in primary hippocampal neurons.

Together, these findings demonstrate bidirectional functional coupling between Ca2+ and NO signals in primary hippocampal neurons

Bioluminescent optogenetics combines optogenetic principles with bioluminescent proteins to visualize and manipulate neural activity in real time and can support efficient, less invasive monitoring of neuronal activity.

MscS showed diminished ultrasound responses at higher stimulation intensities.

Preclinical successes including AAV-mediated rescue of NPHS2-associated nephrotic syndrome and complement modulation in IgA nephropathy support the therapeutic potential of gene-based interventions in podocytopathies.

AAV-based RPGR gene therapy significantly increased ocular treatment-emergent adverse event risk in pooled controlled clinical evidence for RPGR-associated XLRP.

Increasing clinical experience with in vivo editing using LNP- and AAV-based platforms has revealed safety considerations including vector immunogenicity, systemic inflammation, and organ-specific toxicities.

Next-generation editors and targeted delivery systems have expanded the scope of feasible cardiovascular applications, but biological barriers still limit translation to well tolerated durable one-time genomic therapies.

Cell-specific promoters are essential for precise and efficient optogenetic stimulation because they restrict opsin expression to selected target cells.

Emerging editing technologies aim to overcome limited vector cargo capacity, PAM incompatibility, chromatin accessibility, suboptimal editing efficiency, and off-target activity.

Gene therapy has emerged as a transformative approach for podocytopathies using AAV vectors, CRISPR-based editing, and RNA modulation to correct pathogenic mutations or restore disrupted pathways.

The paper reports a bicistronic dual biosensor that combines jGCaMP8s and O-geNOps and is delivered by AAV to primary hippocampal neurons.

Here we report a bicistronic dual biosensor that combines jGCaMP8s for high-sensitivity Ca2+ imaging with the orange fluorescent NO reporter O-geNOps, delivered by adeno-associated virus (AAV) to primary hippocampal neurons.

Immune responses, vector biodistribution, and disease heterogeneity remain challenges for podocytopathy gene therapy.

Successful clinical translation of gene and base editing for cardiovascular disease depends on efficient and precise delivery and on mitigating immunogenicity and toxicity from both delivery vectors and gene-editing enzymes.

Gene delivery approaches may advance conventional antibody therapeutics against viral infections and other diseases through local persistence of the proteins.

Lipid nanoparticle transfection efficiency was significantly higher than lipofectamine in almost all treatments.

Transfection efficiency was significantly higher compared to lipofectamine in almost all treatments.

AAV-based gene therapy has achieved approved clinical use, including Luxturna for a genetic retinal disease.

including the approval of Luxturna for a genetic retinal disease

First-in-human dual AAV therapy for hereditary hearing loss showcased restoration of auditory function in patients.

has showcased the restoration of auditory function for patients

AAV-based therapies such as Elevidys for DMD and Zolgensma for SMA demonstrate functional improvements, although immune responses and hepatotoxicity remain concerns.

Clinically, AAV-based therapies (e.g., Elevidys® for DMD, Zolgensma® for SMA) demonstrate functional improvements, though immune responses and hepatotoxicity remain concerns.

LNP and GalNAc non-viral vectors have led to successful gene therapy products.

non-viral vectors such as lipid nanoparticles (LNP) and N-acetylgalactosamine (GalNAc) have led to successful gene therapy products

Lipid nanoparticles are presented as a promising non-viral platform for optogenetic delivery because they can overcome some AAV-related limitations.

lipid nanoparticles can overcome some of the previously mentioned problems of AAV vectors, making them prime candidates for optogenetic delivery

Non-viral vectors including liposomes, polymers, and exosomes offer advantages in cargo capacity, biocompatibility, and scalable production, but they face challenges in transduction efficiency and endosomal escape.

Non-viral vectors (liposomes, polymers, exosomes) offer advantages in cargo capacity (delivering full-length dystrophin), biocompatibility, and scalable production but face challenges in transduction efficiency and endosomal escape.

AAV transduction was more efficient in pigeon telencephalon than mesencephalon.

AAV transduction being more efficient in the telencephalon than mesencephalon

AAV vectors are presented as the primary delivery platform for DMD gene therapy because of muscle tropism, low immunogenicity, and long-term transgene expression.

Lipid nanoparticles were evaluated for delivery of the ChrimsonR plasmid in neurons in vitro.

we evaluated their suitability for the delivery of the ChrimsonR plasmid in neurons in vitro

DNA sequencing technologies enhance identification and incorporation of therapeutic genes into AAV vectors for ovarian cancer gene therapy.

AAV vectors dominate clinical applications for gene therapy in hereditary skeletal myopathies because they efficiently transduce post-mitotic myofibers and support sustained transgene expression.

Adeno-associated virus (AAV) vectors dominate clinical applications due to their efficient transduction of post-mitotic myofibers and sustained transgene expression.

The duration of AAV-mediated expression is limited by the episomal nature of AAV genomes and their loss during muscle fiber regeneration.

AAV engineering innovations including capsid modification, self-complementary genomes, and tissue-specific promoters such as MHCK7 enhance muscle tropism while mitigating immunogenicity and off-target effects.

Innovations in AAV engineering, such as capsid modification (chemical conjugation, rational design, directed evolution), self-complementary genomes, and tissue-specific promoters (e.g., MHCK7), enhance muscle tropism while mitigating immunogenicity and off-target effects.

The hChR2 component significantly affected transduction efficiency in the pigeon AAV experiments.

the hChR2 component significantly affecting transduction efficiency

Despite substantial progress, safety, immunogenicity, and stability of genetic correction remain unresolved issues in AAV-mediated DMD therapy.

Further in vitro analysis showed altered electrophysiological parameters with reduced signal amplitudes after lipid nanoparticle-mediated delivery.

Further in vitro analysis showed that electrophysiological parameters were altered, with reduced signal amplitudes

Future targeted gene delivery strategies for muscular disorders emphasize AI-driven vector design, AAV-exosome hybrid systems, and standardized manufacturing to pursue single-dose lifelong therapeutic benefit.

Future directions focus on AI-driven vector design, hybrid systems (AAV-exosomes), and standardized manufacturing to achieve "single-dose, lifelong cure" paradigms for muscular disorders.

AAV limitations for delivering CRISPR modalities continue to impede viable therapeutic interventions targeting the brain.

However, AAV limitations for delivering CRISPR modalities continue to impede viable therapeutic interventions targeting the brain.

AAV vectors for gene therapy are limited by the cost and toxicity of the large doses required.

The promise of adeno-associated virus (AAV) vectors for gene therapy is held back by the cost and toxicity of the large doses required.

Major challenges for AAV-mediated DMD gene therapy include immune responses against viral capsid and transgene products and inability to perform repeated administrations.

mRNA platforms, viral vectors, and engineered cell therapies have matured considerably due to years of clinical experience and growing regulatory confidence.

Dual AAV therapy can overcome large gene delivery limitations.

the first-in-human dual AAV therapy for hereditary hearing loss, which overcomes large gene delivery

The study determined optimum injection dose and transduction period guidelines for each location and serotype tested in pigeons.

The optimum injection dose and transduction period guideline for each location and serotype were determined.

Lipid nanoparticles represent a promising non-viral platform for optogenetic delivery, but formulation optimization is required to achieve full functional efficacy.

These results demonstrate that lipid nanoparticles represent a promising non-viral platform for optogenetic delivery, though formulation optimization is required to achieve full functional efficacy.

AAV packaging capacity is approximately 4.7 kb, which necessitates truncated mini- and micro-dystrophin transgenes and compact genome editing systems for DMD applications.

In pigeons, AAV serotypes 1 and 11 with ubiquitous promoters transduced well across all brain regions tested.

We found serotypes 1 and 11 with ubiquitous promoters transducing well at all brain regions

In mice, intraperitoneal AAV injection during the resting phase (ZT6) produced greater transgene expression over several weeks than equivalent injection during the waking phase (ZT18).

intraperitoneal doses of AAVs injected during the resting phase (ZT6, 12:00PM) produced greater transgene expression over several weeks than equivalent doses injected during the waking phase (ZT18, 12:00AM).

AAV vectors have potential for gene therapy in ovarian cancer.

AAV is characterized by high transduction efficiency in dividing and non-dividing cells, low immunogenicity and toxicity, and exceptional tissue specificity.

AAV is characterized by high transduction efficiency in both dividing and non-dividing cells, low immunogenicity and toxicity, and exceptional tissue specificity.

Cell viability assays showed no decline in cell viability after lipid nanoparticle-mediated delivery in vitro.

however, cell viability assays showed no decline in cell viability

In rat cortical neurons, lipid nanoparticles did not reduce several measured neuronal morphological parameters in most tested concentrations compared with lipofectamine.

In rat cortical neurons, in most of the concentrations tested, there was no reduction in several neuron morphological parameters that we measured when compared to another non-viral nanoparticle called lipofectamine.

Rational ovarian cancer AAV gene therapy strategies can be categorized by target cells and target genes to determine effective approaches.

Innovations in AAV capsid design allow targeted delivery focused on ovarian cancer stem cells identified by specific markers.

Timing AAV administration by circadian phase could improve safety and reduce costs of AAV gene therapy and potentially other nanoparticle therapies.

This insight could lead to future work that improves safety and reduces costs of AAV gene therapy and other nanoparticle therapies.

Clinical success of AAV- and lentiviral-based interventions and approval of CAR-T cell therapies highlight the potential of these technologies to transform delivery of antibody therapeutics.

AAV is a promising and widely utilized vector for gene therapy applications including the CNS.

The adeno-associated virus (AAV) is a promising and most widely utilized vector for gene therapy application including the CNS.

Lentiviral vectors, adenoviral vectors, and AAV are widely used viral vectors that have enabled notable preclinical and clinical successes in gene therapy over the past two decades.

Over the past two decades, three widely used viral vectors-lentiviruses (LV), adenoviruses (Ad), and adeno-associated viruses (AAV)-have enabled notable preclinical and clinical successes

This review concerns adeno-associated virus as a delivery vector for gene therapy of human diseases.

The review covers characteristics of different AAV delivery routes in ocular clinical applications.

The review discusses progress of AAV in ocular optogenetic therapy.

The review outlines recent progress in AAV-mediated gene editing and silencing strategies for genetic ocular diseases, especially base editing and prime editing.

AAV is presented as one of the most promising viral gene delivery tools for ocular gene therapy because it can infect various tissue types and is considered relatively safe.

An increasing number of clinical trials of AAV-mediated gene therapy are underway for ocular diseases.

The eye is described as a favorable organ for AAV gene therapy because its limited volume is suitable for small doses that can achieve stable transduction.

The review identifies difficulties in the clinical transformation of AAV-mediated ocular gene therapy.

Viral vehicles combined with genetic tools enable visualization of functional neural networks and monitoring and manipulation of neural circuit functions with cell type- and projection-specific targeting.

Viral vehicles combined with genetic tools provide the possibility to visualize entire functional neural networks and monitor and manipulate neural circuit functions by high-resolution cell type- and projection-specific targeting.

Pairing engineered AAVs with gene regulatory elements and reporter, sensor, or effector cargo enables highly specific transgene expression for anatomical and functional analyses of brain cells and circuits.

AAV vectors have two engineerable features, the capsid and the cargo, which can be modified to alter tropism and transgene expression control.

The review presents a comprehensive capsid-and-cargo AAV toolkit for genetic access to molecularly defined brain cell types.

The review summarizes current and emerging viral strategies for targeting neural circuits with a focus on AAV vectors.

In this review, we summarize current and emerging viral strategies for targeting neural circuits and focus on adeno-associated virus (AAV) vectors.

Recombinant AAVs are commonly used gene delivery vehicles for neuroscience research.

Intersectional AAV circuit-targeting approaches can target expression of fluorescent reporters, optogenetic ion channels, chemogenetic receptors, disease-associated proteins, and other factors to defined neural circuits.

These approaches can precisely target the expression of fluorescent reporters, optogenetic ion channels, chemogenetic receptors, disease-associated proteins, and other factors to defined neural circuits

The review covers axonal-transport-based intersectional AAV approaches for targeting neuron populations defined by connectivity.

We review emerging techniques that use the axonal transport of adeno-associated virus (AAV) vectors to dissect neural circuits. These intersectional approaches specifically target AAV-mediated gene expression to discrete neuron populations based on their axonal connectivity

AAV1-mediated anterograde transsynaptic tagging is presented in the supplied source summary as a basis for input-defined and input-plus-output-defined circuit targeting schemes discussed by the review.

forming the basis of input-defined and input+output-defined circuit targeting schemes discussed in the review

AAV2-retro is presented in the supplied source summary as a key engineered retrograde capsid enabling output-defined intersectional targeting strategies discussed by the review.

the engineered retrograde capsid AAV2-retro (Tervo et al., 2016)

INTRSECT is presented in the supplied source summary as a multi-recombinase Boolean expression framework connected to reviewed intersectional AAV approaches.

introducing the multi-recombinase Boolean expression framework explicitly connected to reviewed intersectional AAV approaches

Genetically modified viral vectors broaden the ability to express genes of interest and support inducible manipulations in neural systems.

Chemogenetics can be activated via a systemic drug without indwelling fiber optics and acts in a more naturalistic modulatory fashion through second-messenger pathways than optogenetics.

Optogenetic and chemogenetic approaches allow mechanistic, temporally specific, cell-type-specific, and circuit-specific neural regulation of behaviors.

Smaller Cas9 orthologues enabled packaging of Cas9 nuclease and its chimeric guide RNA into a single AAV delivery vehicle for robust in vivo genome editing.

Recent discoveries of smaller Cas9 orthologues have enabled the packaging of Cas9 nuclease and its chimeric guide RNA into a single AAV delivery vehicle for robust in vivo genome editing.

Smaller Cas9 orthologues enabled packaging of Cas9 nuclease and its chimeric guide RNA into a single AAV delivery vehicle for robust in vivo genome editing.

Recent discoveries of smaller Cas9 orthologues have enabled the packaging of Cas9 nuclease and its chimeric guide RNA into a single AAV delivery vehicle for robust in vivo genome editing.

Smaller Cas9 orthologues enabled packaging of Cas9 nuclease and its chimeric guide RNA into a single AAV delivery vehicle for robust in vivo genome editing.

Recent discoveries of smaller Cas9 orthologues have enabled the packaging of Cas9 nuclease and its chimeric guide RNA into a single AAV delivery vehicle for robust in vivo genome editing.

Smaller Cas9 orthologues enabled packaging of Cas9 nuclease and its chimeric guide RNA into a single AAV delivery vehicle for robust in vivo genome editing.

Recent discoveries of smaller Cas9 orthologues have enabled the packaging of Cas9 nuclease and its chimeric guide RNA into a single AAV delivery vehicle for robust in vivo genome editing.

Smaller Cas9 orthologues enabled packaging of Cas9 nuclease and its chimeric guide RNA into a single AAV delivery vehicle for robust in vivo genome editing.

Recent discoveries of smaller Cas9 orthologues have enabled the packaging of Cas9 nuclease and its chimeric guide RNA into a single AAV delivery vehicle for robust in vivo genome editing.

Smaller Cas9 orthologues enabled packaging of Cas9 nuclease and its chimeric guide RNA into a single AAV delivery vehicle for robust in vivo genome editing.

Recent discoveries of smaller Cas9 orthologues have enabled the packaging of Cas9 nuclease and its chimeric guide RNA into a single AAV delivery vehicle for robust in vivo genome editing.

Smaller Cas9 orthologues enabled packaging of Cas9 nuclease and its chimeric guide RNA into a single AAV delivery vehicle for robust in vivo genome editing.

Recent discoveries of smaller Cas9 orthologues have enabled the packaging of Cas9 nuclease and its chimeric guide RNA into a single AAV delivery vehicle for robust in vivo genome editing.

The combined use of small Cas9 orthologues, tissue-specific minimal promoters, AAV serotypes, and different routes of administration has advanced efficient and precise in vivo genome editing.

the combined use of small Cas9 orthologues, tissue-specific minimal promoters, AAV serotypes, and different routes of administration has advanced the development of efficient and precise in vivo genome editing

The combined use of small Cas9 orthologues, tissue-specific minimal promoters, AAV serotypes, and different routes of administration has advanced efficient and precise in vivo genome editing.

the combined use of small Cas9 orthologues, tissue-specific minimal promoters, AAV serotypes, and different routes of administration has advanced the development of efficient and precise in vivo genome editing

The combined use of small Cas9 orthologues, tissue-specific minimal promoters, AAV serotypes, and different routes of administration has advanced efficient and precise in vivo genome editing.

the combined use of small Cas9 orthologues, tissue-specific minimal promoters, AAV serotypes, and different routes of administration has advanced the development of efficient and precise in vivo genome editing

The combined use of small Cas9 orthologues, tissue-specific minimal promoters, AAV serotypes, and different routes of administration has advanced efficient and precise in vivo genome editing.

the combined use of small Cas9 orthologues, tissue-specific minimal promoters, AAV serotypes, and different routes of administration has advanced the development of efficient and precise in vivo genome editing

The combined use of small Cas9 orthologues, tissue-specific minimal promoters, AAV serotypes, and different routes of administration has advanced efficient and precise in vivo genome editing.

the combined use of small Cas9 orthologues, tissue-specific minimal promoters, AAV serotypes, and different routes of administration has advanced the development of efficient and precise in vivo genome editing

The combined use of small Cas9 orthologues, tissue-specific minimal promoters, AAV serotypes, and different routes of administration has advanced efficient and precise in vivo genome editing.

the combined use of small Cas9 orthologues, tissue-specific minimal promoters, AAV serotypes, and different routes of administration has advanced the development of efficient and precise in vivo genome editing

The combined use of small Cas9 orthologues, tissue-specific minimal promoters, AAV serotypes, and different routes of administration has advanced efficient and precise in vivo genome editing.

the combined use of small Cas9 orthologues, tissue-specific minimal promoters, AAV serotypes, and different routes of administration has advanced the development of efficient and precise in vivo genome editing

AAV delivery vehicles and CRISPR components are associated with off-target effects, immunogenicity, and toxicity as challenges for therapeutic use.

potential strategies to overcome off-target effects, immunogenicity, and toxicity associated with CRISPR components and AAV delivery vehicles

AAV delivery vehicles and CRISPR components are associated with off-target effects, immunogenicity, and toxicity as challenges for therapeutic use.

potential strategies to overcome off-target effects, immunogenicity, and toxicity associated with CRISPR components and AAV delivery vehicles

AAV delivery vehicles and CRISPR components are associated with off-target effects, immunogenicity, and toxicity as challenges for therapeutic use.

potential strategies to overcome off-target effects, immunogenicity, and toxicity associated with CRISPR components and AAV delivery vehicles

AAV delivery vehicles and CRISPR components are associated with off-target effects, immunogenicity, and toxicity as challenges for therapeutic use.

potential strategies to overcome off-target effects, immunogenicity, and toxicity associated with CRISPR components and AAV delivery vehicles

AAV delivery vehicles and CRISPR components are associated with off-target effects, immunogenicity, and toxicity as challenges for therapeutic use.

potential strategies to overcome off-target effects, immunogenicity, and toxicity associated with CRISPR components and AAV delivery vehicles

AAV delivery vehicles and CRISPR components are associated with off-target effects, immunogenicity, and toxicity as challenges for therapeutic use.

potential strategies to overcome off-target effects, immunogenicity, and toxicity associated with CRISPR components and AAV delivery vehicles

AAV delivery vehicles and CRISPR components are associated with off-target effects, immunogenicity, and toxicity as challenges for therapeutic use.

potential strategies to overcome off-target effects, immunogenicity, and toxicity associated with CRISPR components and AAV delivery vehicles

AAV provides a suitable viral vector to package, deliver, and express CRISPR components for targeted gene editing.

AAV provides one of the most suitable viral vectors to package, deliver, and express CRISPR components for targeted gene editing.

AAV provides a suitable viral vector to package, deliver, and express CRISPR components for targeted gene editing.

AAV provides one of the most suitable viral vectors to package, deliver, and express CRISPR components for targeted gene editing.

AAV provides a suitable viral vector to package, deliver, and express CRISPR components for targeted gene editing.

AAV provides one of the most suitable viral vectors to package, deliver, and express CRISPR components for targeted gene editing.

AAV provides a suitable viral vector to package, deliver, and express CRISPR components for targeted gene editing.

AAV provides one of the most suitable viral vectors to package, deliver, and express CRISPR components for targeted gene editing.

AAV provides a suitable viral vector to package, deliver, and express CRISPR components for targeted gene editing.

AAV provides one of the most suitable viral vectors to package, deliver, and express CRISPR components for targeted gene editing.

AAV provides a suitable viral vector to package, deliver, and express CRISPR components for targeted gene editing.

AAV provides one of the most suitable viral vectors to package, deliver, and express CRISPR components for targeted gene editing.

AAV provides a suitable viral vector to package, deliver, and express CRISPR components for targeted gene editing.

AAV provides one of the most suitable viral vectors to package, deliver, and express CRISPR components for targeted gene editing.

DREADD technology is presented as the most robust model of chemogenetics.

Anterograde projection targeting and retrograde transport of viral vectors are two projection-targeting approaches for probing neural circuits.

We discuss two projection targeting approaches for probing neural circuits: anterograde projection targeting and retrograde transport of viral vectors.

Cell type-specific promoters and other nucleotide sequences can be used in viral vectors to target neuronal types at the transcriptional level.

cell type-specific promoters and other nucleotide sequences that can be used in viral vectors to target neuronal types at the transcriptional level

Targeting specific neuronal types with optogenetic and chemogenetic tools remains challenging in primates.

In primates, however, targeting specific types of neurons with these tools remains challenging.

Viral-vector targeting performance is discussed in terms of cell-type tropism and prospects for improved efficacy and selectivity through new variants.

their tropism for different cell types, and prospects for new variants with improved efficacy and selectivity

AAV and lentiviral vectors are major viral-vector platforms discussed for gene delivery to neurons in the adult primate central nervous system.

We review the literature on viral vectors for gene delivery to neurons, focusing on adeno-associated viral vectors and lentiviral vectors

This paper is about AAV at its 50-year milestone.

AAV has shown success in some clinical and research applications.

some of the clinical and research applications where AAV has shown success

AAV is capable of transducing a wide range of species and tissues in vivo.

It is capable of transducing a wide range of species and tissues in vivo

AAV generates relatively mild innate and adaptive immune responses.

and it generates relatively mild innate and adaptive immune responses

AAV shows no evidence of toxicity in the abstract's summarized in vivo context.

with no evidence of toxicity

AAV was adapted for use as a gene transfer vehicle.

Adeno-associated virus (AAV) is a small, nonenveloped virus that was adapted 30 years ago for use as a gene transfer vehicle.

Adeno-associated viruses and lentiviruses have shown promise for delivering targeted genetic interventions in epilepsy gene therapy.

viral vectors, such as adeno-associated viruses and lentiviruses, have shown promise in delivering targeted genetic interventions

Source: Gene therapy for epilepsy: An emerging, promising approach for a serious neurological disorder.

The approved viral gene therapy products highlighted in the abstract rely on adeno-associated vectors and lentiviral vectors for delivery.

Source: CRISPR-Cas editing technologies for viral-mediated gene therapies of human diseases: Mechanisms, progress, and challenges.

The review discusses AAVs, LNPs, lentivirus, and virus-like particles as emerging delivery vehicles for gene editing therapies targeting lipid metabolism in cardiovascular disease.

Emerging delivery vehicles (AAVs, LNPs, lentivirus, virus-like particles) and their translational implications are discussed.

Source: Gene Editing Therapies Targeting Lipid Metabolism for Cardiovascular Disease: Tools, Delivery Strategies, and Clinical Progress.

Adeno-associated viruses are presented as a promising clinical delivery approach for opsins to target cells and can improve flexibility and accuracy of opsin delivery when combined with cell-specific promoters and serotype choice.

Source: Optogenetic approaches for neural tissue regeneration: A review of basic optogenetic principles and target cells for therapy.

Improvements in viral-mediated gene transfer efficiency and clinical-scale manufacturing have helped propel the clinical adoption of gene therapy products.

Source: CRISPR-Cas editing technologies for viral-mediated gene therapies of human diseases: Mechanisms, progress, and challenges.

Nearly 30 new viral gene therapy programs have been approved by the US FDA since the first AAV-based gene therapy approval in 2017.

Source: CRISPR-Cas editing technologies for viral-mediated gene therapies of human diseases: Mechanisms, progress, and challenges.

Major challenges for epilepsy gene therapy include safe and efficient gene delivery, maintaining long-term therapeutic effects, and mitigating potential side effects.

However, significant challenges exist, including ensuring safe and efficient gene delivery, maintaining long-term therapeutic effects, and mitigating potential side effects.

Source: Gene therapy for epilepsy: An emerging, promising approach for a serious neurological disorder.

AAV-based RPGR gene therapy significantly increased ocular treatment-emergent adverse event risk in pooled controlled clinical evidence for RPGR-associated XLRP.

Source: Efficacy and Safety of Gene Therapy for RPGR Gene-Associated X-Linked Retinitis Pigmentosa: A Systematic Review and Meta-Analysis.

Increasing clinical experience with in vivo editing using LNP- and AAV-based platforms has revealed safety considerations including vector immunogenicity, systemic inflammation, and organ-specific toxicities.

Source: Advancing gene and base editing for cardiovascular disease: overcoming barriers in delivery, precision and safety.

Next-generation editors and targeted delivery systems have expanded the scope of feasible cardiovascular applications, but biological barriers still limit translation to well tolerated durable one-time genomic therapies.

Source: Advancing gene and base editing for cardiovascular disease: overcoming barriers in delivery, precision and safety.

Emerging editing technologies aim to overcome limited vector cargo capacity, PAM incompatibility, chromatin accessibility, suboptimal editing efficiency, and off-target activity.

Source: Advancing gene and base editing for cardiovascular disease: overcoming barriers in delivery, precision and safety.

Successful clinical translation of gene and base editing for cardiovascular disease depends on efficient and precise delivery and on mitigating immunogenicity and toxicity from both delivery vectors and gene-editing enzymes.

Source: Advancing gene and base editing for cardiovascular disease: overcoming barriers in delivery, precision and safety.

AAVs and lentiviruses have been used for gene delivery in preclinical and clinical studies.

Adeno-associated viruses (AAVs) and lentiviruses have been used for gene delivery in preclinical and clinical studies

Source: Viral and non-viral cellular therapies for neurodegeneration.

AAV limitations for delivering CRISPR modalities continue to impede viable therapeutic interventions targeting the brain.

However, AAV limitations for delivering CRISPR modalities continue to impede viable therapeutic interventions targeting the brain.

Source: Trends and challenges of AAV-delivered gene editing therapeutics for CNS disorders: Implications for neurodegenerative disease.

AAV is characterized by high transduction efficiency in dividing and non-dividing cells, low immunogenicity and toxicity, and exceptional tissue specificity.

AAV is characterized by high transduction efficiency in both dividing and non-dividing cells, low immunogenicity and toxicity, and exceptional tissue specificity.

Source: Trends and challenges of AAV-delivered gene editing therapeutics for CNS disorders: Implications for neurodegenerative disease.

Current and developing therapeutic strategies for neurodegeneration include viral vector-based gene delivery, antisense oligonucleotide and RNA interference methods, stem cell transplantation, and genome editing technologies.

In this review, we describe current and developing therapeutic strategies that include viral vector-based gene delivery, antisense oligonucleotide (ASO) and RNA interference methods, stem cell transplantation, and genome editing technologies.

Source: Viral and non-viral cellular therapies for neurodegeneration.

AAV is a promising and widely utilized vector for gene therapy applications including the CNS.

The adeno-associated virus (AAV) is a promising and most widely utilized vector for gene therapy application including the CNS.

Source: Trends and challenges of AAV-delivered gene editing therapeutics for CNS disorders: Implications for neurodegenerative disease.

This review concerns adeno-associated virus as a delivery vector for gene therapy of human diseases.

Source: Adeno-associated virus as a delivery vector for gene therapy of human diseases

The review covers characteristics of different AAV delivery routes in ocular clinical applications.

Source: AAV for Gene Therapy in Ocular Diseases: Progress and Prospects

The review discusses progress of AAV in ocular optogenetic therapy.

Source: AAV for Gene Therapy in Ocular Diseases: Progress and Prospects