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The AAV capsid can influence the epigenetic marking of rAAV delivered episomal genomes in a species dependent manner

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE226268 | GEO | 2023/02/28

REPOSITORIES: GEO

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The AAV capsid can influence the epigenetic marking of rAAV delivered episomal genomes in a species dependent manner [CnT_InVivo]

Project description:Recombinant adeno-associated viral vectors (rAAVs) are among the most commonly used vehicles for in vivo based gene therapies. However, it is hard to predict which AAV capsid will provide the most robust expression in human subjects due to the observed discordance in vector-mediated transduction between species. We used a primate specific capsid, AAV-LK03, and demonstrated that the limitation of this capsid towards transduction of mouse cells was unrelated to cell entry and nuclear transport but rather due to depleted histone H3 chemical modifications related to active transcription, namely H3K4me3 and H3K27ac, on the vector DNA itself. A single-amino acid insertion into the AAV-LK03 capsid enabled efficient transduction and the accumulation of active-related epigenetic marks on the vector chromatin in mouse without compromising transduction efficiency in human cells. Our study suggests that the capsid protein itself is involved in driving the epigenetic status of the vector genome, most likely during the process of uncoating. Programming viral chromatin states by capsid design may enable facile DNA transduction between vector and host species and ultimately led to rationale selection of AAV capsids for use in humans.

2023-02-28 | GSE226167 | GEO

The AAV capsid can influence the epigenetic marking of rAAV delivered episomal genomes in a species dependent manner [Tn5_InVivo]

2023-02-28 | GSE226165 | GEO

The AAV capsid can influence the epigenetic marking of rAAV delivered episomal genomes in a species dependent manner [Tn5_InVitro]

2023-02-28 | GSE226164 | GEO

The AAV capsid can influence the epigenetic marking of rAAV delivered episomal genomes in a species dependent manner [CnT_InVitro]

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The AAV capsid can influence the epigenetic marking of rAAV delivered episomal genomes in a species dependent manner

Project description:The AAV capsid can influence the epigenetic marking of rAAV delivered episomal genomes in a species dependent manner

| PRJNA939495 | ENA

The AAV capsid can influence the epigenetic marking of rAAV delivered episomal genomes in a species dependent manner [Tn5_InVitro]

Project description:The AAV capsid can influence the epigenetic marking of rAAV delivered episomal genomes in a species dependent manner [Tn5_InVitro]

| PRJNA939193 | ENA

The AAV capsid can influence the epigenetic marking of rAAV delivered episomal genomes in a species dependent manner [CnT_InVitro]

Project description:The AAV capsid can influence the epigenetic marking of rAAV delivered episomal genomes in a species dependent manner [CnT_InVitro]

| PRJNA939443 | ENA

The AAV capsid can influence the epigenetic marking of rAAV delivered episomal genomes in a species dependent manner [Tn5_InVivo]

Project description:The AAV capsid can influence the epigenetic marking of rAAV delivered episomal genomes in a species dependent manner [Tn5_InVivo]

| PRJNA939192 | ENA

The AAV capsid can influence the epigenetic marking of rAAV delivered episomal genomes in a species dependent manner [CnT_InVivo]

Project description:The AAV capsid can influence the epigenetic marking of rAAV delivered episomal genomes in a species dependent manner [CnT_InVivo]

| PRJNA939199 | ENA

rAAV-delivered PTEN therapeutics for prostate cancer.

Project description:Effective treatments for prostate cancer (PCa) require further development, and previous studies have reported that PTEN and its downstream target CDKN1B are significantly downregulated in PCa cells compared with normal cells. Therefore, modulation of PTEN and CDKN1B expression might be a promising therapeutic approach for PCa treatment. Expression of PTEN and CDKN1B was verified in specimens from PCa patients and transgenic adenocarcinoma mouse prostate (TRAMP) mice. The effect of PTEN on PCa cell migration, apoptosis, and the cell cycle was analyzed in vitro using a wound-healing assay and flow cytometry. We assessed the ability of intraprostatic and intratumoral injections of recombinant adeno-associated virus (rAAV) 9 expressing Pten or Cdkn1b into TRAMP mice and a subcutaneous tumor xenograft mouse model, respectively, to inhibit PCa progression. PTEN and CDKN1B were significantly downregulated in human and mouse PCa samples, and CDKN1B expression correlated positively with PTEN expression. PTEN overexpression significantly inhibited cell migration and cell-cycle progression and promoted apoptosis in PCa cells by decreasing Ccnd1 expression and increasing that of Cdkn1b. Importantly, treatment with the rAAV9.Pten or rAAV9.Cdkn1b extended the lifespan of TRAMP mice and inhibited the growth rate of tumor xenografts by regulating downstream gene expression. Moreover, neoplasia in treated prostates was significantly diminished compared with that in control prostates, and apoptosis was markedly observed in xenografts treated with Pten or Cdkn1b. These data indicate that rAAV-based PTEN/CDKN1B delivery is promising for the development of novel therapeutics for PCa.

| S-EPMC8671520 | biostudies-literature

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