Comparative analysis of the transduction efficiency of five adeno associated virus serotypes and VSV-G pseudotype lentiviral vector in lung cancer cells

Chen, Chiachen; Akerstrom, Victoria; Baus, James; Lan, Michael S.; Breslin, Mary B.

doi:10.1186/1743-422x-10-86

Cited by 19 publications

(11 citation statements)

References 23 publications

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“… 30 , 31 So far, only a few studies have demonstrated in vivo gene editing following LV delivery of Cas9. 31 , 32 , 33 , 34 In this study, we chose LV as the delivery tool and suggested a better therapeutic efficacy over the renewal cycle of the epidermis. Then, the disrupted cytoskeletal integrity, abnormal differentiation, and irregular proliferation were ameliorated.…”

Section: Discussionmentioning

confidence: 99%

CRISPR/Cas9-Mediated Treatment Ameliorates the Phenotype of the Epidermolytic Palmoplantar Keratoderma-like Mouse

Luan

Chen

Tang

et al. 2018

Molecular Therapy - Nucleic Acids

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CRISPR/Cas9 has been confirmed as a distinctly efficient, simple-to-configure, highly specific genome-editing tool that has been used to treat monogenetic disorders. Epidermolytic palmoplantar keratoderma (EPPK) is a common autosomal dominant keratin disease resulting from dominant-negative mutation of the KRT9 gene, and it has no effective therapy. We performed CRISPR/Cas9-mediated treatment on a knockin (KI) transgenic mouse model that carried a small indel heterozygous mutation of Krt9, c.434delAinsGGCT (p.Tyr144delinsTrpLeu), which caused a humanized EPPK-like phenotype. The mutation within exon 1 of Krt9 generated a novel protospacer adjacent motif site, TGG, for Cas9 recognition and cutting. By delivering lentivirus vectors (LVs) encoding single-guide RNAs (sgRNAs) and Cas9 that targeted Krt9 sequence into HeLa cells engineered to constitutively express wild-type and mutant keratin 9 (K9), we found the sgRNA was highly effective in reducing expression of the mutant K9 protein in vitro. We injected the LV into the fore-paws of adult KI-Krt9 mice three times every 8 days and found that the expression of K9 decreased ∼14.6%. The phenotypic mitigation was revealed by restoration of the abnormal differentiation and aberrant proliferation of the epidermis. Our data are the first to show that CRISPR/Cas9 is a potentially powerful therapeutic option for EPPK and other PPK subtypes.

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Section: Discussionmentioning

confidence: 99%

CRISPR/Cas9-Mediated Treatment Ameliorates the Phenotype of the Epidermolytic Palmoplantar Keratoderma-like Mouse

Luan

Chen

Tang

et al. 2018

Molecular Therapy - Nucleic Acids

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“…To date, AAV serotype 2 (AAV2) is the most commonly used AAV vector already used in clinical trials. Tumor cell in vitro transduction with different AAV serotypes of a variety of human cells has been reported, but there is still much controversy with reference to the transduction efficiency of AAV vectors in human malignant cells [38][39][40]. However, there are certain problems associated with viral vectors for cancer gene therapy.…”

Section: Discussionmentioning

confidence: 99%

Recovery HLA-A2 and Beta2-microglobulin Expression in Tumor Cells Using Viral Vectors

Fj¹,

A²,

Zinchenko³

et al. 2017

J Cancer Sci Ther

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Background: Tumor elimination and the success of cancer immunotherapy depend on the proper expression of HLA class I complex (HLA-I) required for the presentation of tumor-associated peptides to cytotoxic T-lymphocytes. Tumors escape immune attack by losing HLA-I expression, often due to irreversible genetic/chromosomal alterations, including mutations in beta2-microglobulin (B2M) or lack of HLA-A2 allele due to a haplotype loss. The introduction of these genes and re-expression of the missing HLA-I specificity on the tumor cell surface is an attractive strategy to induce tumor rejection by T-lymphocytes. Methods:Using genomic HLA-I typing and gene sequencing we determined HLA-I phenotypes and alterations in different human tumor cell lines previously characterized in our laboratory. We used adeno-and adeno-associated viruses to reconstitute/up-regulate HLA-A2 or/and B2M expression in these cells in vitro. Using flow cytometry and immunocytochemistry we evaluated levels and patterns of HLA-I expression in these cells. Results:We have defined altered HLA-I genotypes in various human tumor cell lines. Ad5 and, to a lesser degree, AAV2 vectors were efficient in a replacement of mutated B2M, recovery of lost endogenous HLA-A2 allele, and de novo expression of an additional HLA-A2 allele in tumor cells naturally lacking HLA-A2. Ad5-mediated co-transfection of both HLA-A2 and B2M demonstrated that the de novo expressed proteins associate to form a detectable HLA-I/B2M complex on the cell surface. Conclusion:Using gene therapy, it is possible to recover normal B2M and HLA-A2 gene expression caused by structural "hard" alteration and to induce co-expression of both genes in cells naturally lacking HLA-A2 allele. In addition, we demonstrated that transfected tumor cells are able to express seven HLA-I alleles. The recovery of the missing HLA-I molecules in tumor cells using adeno and adeno-associated viruses can be a useful strategy to circumvent cancer immune escape and increase tumor rejection.

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“…Genes chosen for delivery are diverse and have shown different results; the myogenic regulation involving myostatin and follistatin genes has been extensively studied. There is a tendency to use the AAV [17], and it is emerging as one of the most popular gene delivery systems because of a lack of pathogenicity in humans, mild immune response, and its long-term and efficient transgene expression in various cells [18]. Some AAVs do not integrate into the cell genome and can exist long term in non-dividing cells.…”

Section: Gene Therapymentioning

confidence: 99%

Gene and cell therapy for muscle regeneration

Stilhano

Silva

Ingham

et al. 2015

Curr Rev Musculoskelet Med

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Skeletal muscle injury and healing are multifactorial processes, involving three steps of healing: (1) degeneration and inflammation, (2) regeneration, and (3) fibrosis. Fibrous tissue hinders the muscle's complete recovery and current therapies fail in achieving total muscle recovery. Gene and cell therapy (or both) are potential future treatments for severe muscular injuries. Stem cells' properties associated with growth factors or/ and cytokines can improve muscle healing and permit long-term recovery.

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Comparative analysis of the transduction efficiency of five adeno associated virus serotypes and VSV-G pseudotype lentiviral vector in lung cancer cells

Cited by 19 publications

References 23 publications

CRISPR/Cas9-Mediated Treatment Ameliorates the Phenotype of the Epidermolytic Palmoplantar Keratoderma-like Mouse

CRISPR/Cas9-Mediated Treatment Ameliorates the Phenotype of the Epidermolytic Palmoplantar Keratoderma-like Mouse

Recovery HLA-A2 and Beta2-microglobulin Expression in Tumor Cells Using Viral Vectors

Gene and cell therapy for muscle regeneration

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