Cell and gene therapy (CGT) has a variety of potential applications in human immunodeficiency virus (HIV) prevention and management. The existing network of CGT researchers for HIV cure will benefit from an influx of fresh ideas and energy from CGT researchers keen to embrace a new challenge for an old virus.

Cardiac hypertrophy is a major risk factor for congestive heart failure, a leading cause of morbidity and mortality. Abrogating hypertrophic progression is a well-recognized therapeutic goal. Mitochondrial dysfunction is a hallmark of numerous human diseases, including cardiac hypertrophy and heart failure. F1Fo-ATP synthase catalyzes the final step of oxidative energy production in mitochondria. Oligomycin

Viral-mediated gene augmentation offers tremendous promise for the treatment of inherited retinal diseases. The development of effective gene therapy requires an understanding of the vector’s tissue-specific behavior, which may vary depending on serotype, route of delivery, or target species. Using an ex vivo organotypic explant system, we previously demonstrated that retinal tropism and transduction

The lung has long been a target for gene therapy, yet efficient delivery and phenotypic disease correction has remained challenging. Although there have been significant advancements in gene therapies of other organs, including the development of several ex vivo therapies, in vivo therapeutics of the lung have been slower to transition to the clinic. Within the past few years, the field has witnessed

Less than 20% of the protein coding genome is thought to be targetable using small molecules. mRNA therapies are not limited in the same way since in theory, they can silence or edit any gene by encoding CRISPR nucleases, or alternatively, produce any missing protein. Yet not all mRNA therapies are equally likely to succeed. Over the past several years, an increasing number of clinical trials with

Cystic fibrosis (CF) is an autosomal recessive disease caused by variations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Although CF affects multiple organs, the primary cause of mortality is respiratory failure resulting from poor clearance of hyperviscous secretions and subsequent airway infection. Recently developed CFTR modulators provide significant therapeutic benefit

The promise of genetic therapies has turned into reality in recent years, with new first-line treatments for fatal diseases now available to patients. The development and testing of genetic therapies for respiratory diseases such as cystic fibrosis (CF) has also progressed. The addition of gene editing to the genetic agent toolbox, and its early success in other organ systems, suggests we will see

The list of successful gene therapy trials using adeno-associated virus (AAV)-based vectors continues to grow and includes a wide range of monogenic diseases. Replication incompetent AAV genomes typically remain episomal and expression dilutes as cells divide and die. Consequently, long-term transgene expression from AAV is best suited for quiescent cell types, such as retinal cells, myocytes, or neurons

Efforts to identify mutations that underlie inherited genetic diseases combined with strides in the development of gene therapy vectors over the last three decades have culminated in the approval of several adeno-associated virus (AAV)-based gene therapies. Genetic diseases that manifest in the lung such as cystic fibrosis (CF) and surfactant deficiencies, however, have so far proven to be elusive

To test the effectiveness of repeat dosing, we sprayed two doses (1013 vg each) of AAV1Δ27-264-CFTR into airways of four rhesus monkeys at 0 and 30 days, followed by a single dose of 1013 vg of AAV1GFP on day 60. Monkeys were sacrificed on day 90. No adverse events occurred, indicating that AAV1 vectors are safe. An elevated anti-AAV1 neutralizing titer was established by the third dose. A positive

Hypopharyngeal carcinoma is one of the most aggressive subtypes of squamous cell carcinoma of the head and neck. Although significant progress has been made in surgical techniques, radiotherapy and chemotherapy, the prognosis is still poor. Mesenchymal Stem Cells (MSCs) have attracted substantial attention as tumor-targeted cellular carriers for cancer gene therapy. We have previously shown that recombinant

Recombinant adeno-associated virus (rAAV) vectors have become one of the most promising and efficacious delivery vehicles for human gene therapy; however, low infectivity remains a major ongoing obstacle in clinical application of rAAV vectors. Multiple strategies, including rAAV capsid modification and the application of pharmacological reagents, have been explored to enhance rAAV vector gene delivery

Recently, we established an AAV9 capsid-promoter interaction that directly determined cell-specific gene expression across two synthetic promoters, Cbh and CBA, in the rat striatum. The present studies not only expand this capsid-promoter interaction to include another promoter in the rat striatum, but also establishes AAV capsid-promoter interactions in the non-human primate brain. When AAV9 vectors

The development of genome-editing technology could lead to breakthrough gene therapy. Genome editing has made it possible to easily knock out or modify a target gene, while current gene therapy using a virus vector or plasmid hampering modification with respect to gene replacement therapies. Clinical development using these genome-editing tools is progressing rapidly. However, it is also becoming clear

With conventional treatments for Primary immunodeficiency diseases (PIDs), such as allogeneic stem cell transplantation or autologous gene therapy, still facing important challenges, the rapid development of genome editing technologies to more accurately correct the mutations underlying the onset of genetic disorders has provided a new alternative, yet promising platform for the treatment of such diseases

Recent studies have reported the crucial role of STC2 in hepatocellular carcinoma, however, its role in head and neck squamous cell carcinoma (HNSCC) remains elusive. In the present study, microRNA-206 (miR-206) was predicted to target STC2 gene. The study herein aimed to elucidate the effect of miR-206 on HNSCC by targeting STC2. STC2 was highly expressed in HNSCC tissues and cells. By targeting STC2

Hematopoietic stem cell gene therapy has become a successful therapeutic strategy for some inherited genetic disorders. Nonclinical toxicity studies performed to support the human clinical trials using viral-mediated gene transfer and autologous hematopoietic stem and progenitor cell (HSPC) transplantation are complex and the use of mouse models of human diseases makes interpretation of the results

Oncolytic viruses are promising cancer therapies due to their selective killing of tumor cells and ability to stimulate the host immune system. As an oncolytic virus platform, vaccinia virus has unique advantages, including rapid replication, a broad range of host targets, and a large capacity for transgene incorporation. In this study, we developed a novel oncolytic vaccinia virus with high potency

Recent advances in genome sequencing have greatly improved our ability to understand and identify the causes of genetic diseases. However, there remains an urgent need for innovative, safe, and effective treatments for these diseases. CRISPR-based genome editing systems have become important and powerful tools in the laboratory, and efforts are underway to translate these into patient therapies. Therapeutic

The administration of adeno-associated virus (AAV) vectors to nonhuman primates (NHP) via the blood or cerebrospinal fluid (CSF) can lead to dorsal root ganglion (DRG) pathology. The pathology is minimal to moderate in most cases; clinically silent in affected animals; and characterized by mononuclear cell infiltrates, neuronal degeneration, and secondary axonopathy of central and peripheral axons

Friedreich's ataxia (FA), an autosomal recessive disorder caused by a deficiency in the expression of frataxin (FXN), is characterized by progressive ataxia and hypertrophic cardiomyopathy. Although cardiac dysfunction is the most common cause of mortality in FA, the cardiac disease remains subclinical for most of the clinical course because the neurologic disease limits muscle oxygen demands. Previous

Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by degeneration of motor neurons and muscles, and death is usually a result of impaired respiratory function due to loss of motor neurons that control upper airway muscles and/or the diaphragm. Currently, no cure for ALS exists and treatments to date do not significantly improve respiratory or swallowing function. One cause of ALS

Friedreich's ataxia (FRDA) is the most common inherited form of ataxia in humans. It is caused by severe downregulation of frataxin (FXN) expression instigated by hyperexpansion of the GAA repeats located in intron 1 of the FXN gene. Despite numerous studies focused on identifying compounds capable of stimulating FXN expression, current knowledge regarding cis-regulatory elements involved in FXN gene

In the next decades, gene editing technologies are expected to be used in the treatment and prevention of human diseases. Yet, the future uses of gene editing in medicine are still unknown, including its applicability and effectiveness to the treatment and prevention of infectious diseases, cancer, and monogenic and polygenic hereditary diseases. This study aims to address this gap by analyzing the

We report here the development of oncolytic adenoviruses (Ads) that have reduced toxicity, enhanced tumor tropism, produce strong antitumor response, and can overcome resistance to immune checkpoint inhibitor therapy in breast cancer. We have shown that LyP-1 receptor (p32) is highly expressed on the surface of breast cancer cells and tumors from cancer patients, and that increased stromal expression

The aim is to investigate the genomic characterization of uterine sarcoma for rAd-p53 (Gendicine®) combined with chemotherapy treatment. We recently published an article on 12 cases of uterine sarcomas, which were treated with rAd-p53 combined with chemotherapy. We found that rAd-p53 combined with chemotherapy is effective for various uterine sarcomas. Pretreatment pathological specimens of four uterine

Oncolytic adenoviruses (OAds) are promising agents for cancer therapy, representing a novel therapeutic strategy for pancreatic ductal adenocarcinoma (PDAC). However, there are challenges associated with the successful use of an OAd alone, involving the security of the viral vector and screening of an effective antitumor gene. In the present study, a novel OAd CD55-ST13-tumor necrosis factor-related

Oncolytic viruses are emerging as important tools for immunotherapy for cancer treatment; however, most of the clinically tested oncolytic candidates are still administered by intratumoral injection, and new viruses capable of intravenous injection are urgently needed. The M1 virus is a positive-sense single-stranded RNA virus that belongs to the alphavirus family, and it was identified as an oncolytic

Recombinant Adeno-associated viral vector (rAAV) mobilization is a largely theoretical process in which intact AAV vectors spread or “mobilize” from transduced cells and infect additional cells within, or external, of the initial host. This process can be helper virus-independent (vector alone), or helper virus-dependent [de novo rAAV production facilitated by super-infection of both wild-type AAV

Oncolytic viruses are promising anticancer agents; however, regarding their clinical efficacy, there is still significant scope for improvement. Preclinical in vivo evaluation of oncolytic viruses is mainly based on syngeneic or xenograft tumor models in mice, which is labor-intensive and time-consuming. Currently, a large proportion of developmental work in the research field of oncolytic viruses

Although recombinant adeno-associated virus serotype 8 (AAV8) and serotype 5 (AAV5) vectors have shown efficacy in Phase 1 clinical trials for gene therapy of hemophilia B, it has become increasingly clear that these serotypes are not optimal for transducing primary human hepatocytes. We have previously reported that among the 10 most commonly used AAV serotypes, AAV serotype 3 (AAV3) vectors are the

Brain tumors represent the most common pediatric solid neoplasms and leading cause of childhood cancer-related morbidity and mortality. Although most adult brain tumors are supratentorial and arise in the cerebrum, the majority of pediatric brain tumors are infratentorial and arise in the posterior fossa, specifically the cerebellum. Outcomes from malignant cerebellar tumors are unacceptable despite

Long non-coding RNA taurine up-regulated gene 1 (TUG1) participates in nervous system diseases, but its function in Parkinson’s disease remains unclear. This study explored the function and mechanism of TUG1 in Parkinson’s disease (PD). A PD model was constructed using SH-SY5Y cells induced by 1-methyl-4-phenylpyridinium (MPP+) in vitro and mice treated by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

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The UK Respiratory Gene Therapy Consortium (GTC) The GTC was formed in 2001 from three groups at the Universities of Edinburgh and Oxford and Imperial College, London to explore gene therapy as a therapeutic option for people with cystic fibrosis (CF)1. The gene responsible for CF, Cystic Fibrosis Transmembrane conductance Regulator (CFTR), was identified in 19892 and over 2000 mutations are now known3

Hematopoietic stem and progenitor cell (HSPC)-based ex vivo gene therapy has demonstrated clinical success for X-linked severe combined immunodeficiency (SCID-X1) patients who lack a suitable donor for HSPC transplantation. Nevertheless, this form of treatment is associated with an increased risk of infectious disease complications and genotoxicity mainly due to the conditioning regimen. In addition

The efficiency of gene repair by homologous recombination in the liver is enhanced by CRISP/Cas9 incision near the mutation. Here we explored interventions designed to further enhance in vivo hepatocyte gene repair in a model of hereditary tyrosinemia. A two-AAV system was employed: one virus carried a SpCas9 expression cassette and the other harbored a U6 promoter-driven sgRNA and a fragment of Fah

The neuronal ceroid lipofuscinoses (NCLs), often referred to as Batten disease, are inherited lysosomal storage disorders that represent the most common neurodegeneration during childhood. Symptoms include seizures, vision loss, motor and cognitive decline, and premature death. The development of brain-directed treatments for NCLs has made noteworthy progress in recent years. Clinical trials are currently

Gene augmentation therapy based on subretinal delivery of adeno-associated viral (AAV) vectors is proving to be highly efficient in treating several inherited retinal degenerations. However, due to potential complications and drawbacks posed by subretinal injections, there is a great impetus to find alternative methods of delivering the desired genetic inserts to the retina. One such method is an intravitreal

Mutations in the rhodopsin gene may cause photoreceptor degeneration in autosomal dominant retinitis pigmentosa (ADRP) by dominant negative or toxic gain-of-function mechanisms. Controversy exists as to the mechanism by which the widely studied P23H mutation induces rod cell dysfunction and death. Inherited disease caused by dominant negative mutations may be amenable to treatment using wild-type gene

Recombinant adeno-associated viral (rAAV) vector-mediated gene therapy is being developed to treat X-linked retinitis pigmentosa (XLRP) in patients with mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene. In preparation for a clinical gene therapy trial, we conducted dose range finding (DRF) studies with an AAV2 capsid with three surface tyrosine residues changed to phenylalanine (AAV2tYF)

Adeno-associated viral (AAV) vectors represent an ideal vehicle for human gene transfer. One advantage to the AAV vector system is the availability of multiple naturally occurring serotypes that provide selective tropisms for various target cells. Strategies to enhance the properties of the natural AAV isolates have been developed and can be divided into two approaches, rational design or directed

Lysosomal storage disorders (LSDs) are a group of rare inherited metabolic diseases caused by the malfunction of the lysosomal system, which results in the accumulation of undergraded substrates inside the lysosomes and leads to severe and progressive pathology. Despite there currently being a broad understanding of the molecular defects behind LSDs, curative therapies have been approved for only few

Adeno-associated virus (AAV)-based gene therapy is undergoing major expansion into clinical practice, with two treatments currently being granted Food and Drug Administration (FDA) approval. However, the presence of pre-existing neutralizing antibodies (NAB) is one of the significant hurdles for the clinical application of AAV vectors that significantly limits the patient population, which benefits

Adeno-associated virus (AAV) is the most commonly used viral vector for both biological and gene therapeutic applications. Although many methods have been developed to measure quantity attributes of AAV, they are often technically challenging and time-consuming. Here, we report a method to titer AAV with GelGreen® dye, a safe green fluorescence nucleic acid dye recently engineered by Biotium company

Not applicable (This is an invited editoral for the August issue of HGT).

letter to editors do not require abstracts

High interleukin 17A (IL-17A) expression in hepatocellular carcinoma (HCC) tissue promotes HCC development. This study explores a method to inhibit HCC growth by neutralizing IL-17A in the HCC microenvironment. A novel type 5 adenoviral vector (Ad5) that carries DNA sequences encoding specific neutralizing IL-17A recombinant antibody fragments was developed in this research. After locally injecting

Familial hemophagocytic lymphohistiocytosis type 3 (FHL3) is a rare disease caused by mutations to the UNC13D gene and the subsequent absence or decreased activity of the Munc13-4 protein. Munc13-4 is essential for the exocytosis of perforin and granzyme containing granules from cytotoxic cells. Without it, these cells are able to recognize an immunological insult but are unable to execute their cytotoxic