AAV-Mediated Gene Delivery to the Lung

Lieshout, Laura P. van; Domm, Jakob M.; Wootton, Sarah K.

doi:10.1007/978-1-4939-9139-6_21

Cited by 25 publications

(17 citation statements)

References 10 publications

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“…In addition, caprine AAV capsid is 94% similar to the rAAV5 capsid, and has also high transduction efficiency in the above-mentioned cells (89). Van Lieshout et al have indicated the presence of a proteoglycan receptor for laminine, which in the context of our research may explain the increase in the transduction of B16-F10 cells by the hybrid serotype rAAV/DJ in vitro (Figure 3) and in vivo ( Figures 6, 7 and 8) (72). Effective design of gene therapy involves not only the selection of the right vector, but also the selection of the right promoter.…”

Section: Discussionsupporting

confidence: 62%

“…It is a promising method of treatment (administration) and for the identification of cancer cells in the lungs. Its additional advantage is the high safety of administration and the selectivity of gene transfer directly to bronchial tree cells (40,(70)(71)(72)(73). The success of gene therapy is determined by the safe and effective introduction of a therapeutic transgene into cells (74).…”

Section: Discussionmentioning

confidence: 99%

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Mosaic Recombinant Adeno-associated Virus Vector rAAV/DJ/CAG for Targeted Gene Delivery to Melanoma Cells Metastasized to the Lung

et al. 2020

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Background/Aim: Patients with metastasized melanoma have limited treatment options and poor diagnosis. Therefore, the development of treatments requires a new therapeutic approach, of which gene therapy using rAAV vectors can be proposed. The aim of the study was to examine the efficiency of the rAAV vector to transduce mouse melanoma cells both in vitro and in vivo. Materials and Methods: Different rAAV serotypes encoding GFP under the control of both chicken beta-actin and cytomegalovirus promoters were used in the experiments. Intranasal, intraperitoneal, intravenous and intratumoral pathways of administration of rAAV vectors were tested using quantitative-PCR and immunohistochemical staining. Results: The highest transduction efficiency in metastatic cells in vivo was observed 7 days after intranasal administration of a 10 10 gc/0.03 ml dose of rAAV/DJ-CAG. Conclusion: Melanoma gene therapy based on rAAV vectors is a possible treatment option. Melanoma is a tumor that derives from pigment cellsmelanocytes, which develop from the neural tissue of integuments. The most common starting point of melanoma is the skin, but it may also be formed within the mucous membranes of the gastrointestinal tract or in the eyeball. It is a cancer with a high potential for metastasis (1, 2). Despite the progress in anti-cancer treatment, the number of deaths due to metastatic melanoma is still increasing and from the beginning of 2019 circa 7,000 patients in the USA died of it (1). Its aggressiveness causes as much as 90% of deaths among all skin cancers (3). The median survival of patients with melanoma who have distant metastases is shorter than 1 year (4). In the initial stage, the disease is curable, but unfortunately in the advanced stage, when metastasis occurs, it is practically incurable (5). The treatment, which has so far been proposed for the advanced stage, does not provide the desired benefit and the survival of these patients remains unsatisfactory. For instance, the annual survival rate after treatment with targeted therapy for the dual BRAF/MEK mutation is only about 50-60% (4, 6). Therefore, one of the future therapeutic approaches in the treatment of metastatic melanoma can be gene therapy using rAAV vectors, especially with the use of hybrid serotypes, which can achieve high efficiency of gene delivery (7-9). AAV viruses are non-pathogenic, small (approx. 25 nm in diameter) and infect both dividing and non-dividing cells. A distinguishing trait of rAAV is also the occurrence of various serotypes, which are characterized by strong tropism to selected cell types, making them ideal candidates for gene therapy (10). rAAV viruses have become increasingly popular in clinical trials (11, 12). In recent years, two pharmaceutical products using rAAV vectors-Glybera (13) and Luxturna (14) have been registered. Recent studies conducted on hybrid/mosaic serotypes have shown a greater transduction efficiency and are more heterogeneous, both in cellular and tissue specificity (15). The new rAAV vectors are created by a num...

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Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Mosaic Recombinant Adeno-associated Virus Vector rAAV/DJ/CAG for Targeted Gene Delivery to Melanoma Cells Metastasized to the Lung

et al. 2020

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“…[32][33][34] Cas13d and crRNAs can also be delivered using adenovirus or adeno-associated virus (AAV). [35][36][37] Such delivery modalities could be administered to populations via a nebulizer system or nasal spray, which may present a convenient and cost-effective form of antivirals in pandemics. In the present study, we used A549 human lung epithelial carcinoma cells to validate the targeting efficiency of SARS-CoV-2 sequences by predicted crRNAs (Figure S3).…”

Section: Limitations Of Studymentioning

confidence: 99%

A comprehensive analysis and resource to use CRISPR-Cas13 for broad-spectrum targeting of RNA viruses

Lin

Liu

Chemparathy

et al. 2021

Cell Reports Medicine

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“…All AAV6.2FF vectors were generated by plasmid transfection of adherent HEK293 cells using polyethylenimine at the University of Guelph 49 , except for the AAV6.2FF-murine SP-B cDNA (AAV-mSPB) vector used in the intubation (Supplementary Fig. 8c ) and high dose (Fig.…”

Section: Methodsmentioning

confidence: 99%

A lung tropic AAV vector improves survival in a mouse model of surfactant B deficiency

Kang

Lieshout

et al. 2020

Nat Commun

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Surfactant protein B (SP-B) deficiency is an autosomal recessive disorder that impairs surfactant homeostasis and manifests as lethal respiratory distress. A compelling argument exists for gene therapy to treat this disease, as de novo protein synthesis of SP-B in alveolar type 2 epithelial cells is required for proper surfactant production. Here we report a rationally designed adeno-associated virus (AAV) 6 capsid that demonstrates efficiency in lung epithelial cell transduction based on imaging and flow cytometry analysis. Intratracheal administration of this vector delivering murine or human proSFTPB cDNA into SP-B deficient mice restores surfactant homeostasis, prevents lung injury, and improves lung physiology. Untreated SP-B deficient mice develop fatal respiratory distress within two days. Gene therapy results in an improvement in median survival to greater than 200 days. This vector also transduces human lung tissue, demonstrating its potential for clinical translation against this lethal disease.

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AAV-Mediated Gene Delivery to the Lung

Cited by 25 publications

References 10 publications

Mosaic Recombinant Adeno-associated Virus Vector rAAV/DJ/CAG for Targeted Gene Delivery to Melanoma Cells Metastasized to the Lung

Mosaic Recombinant Adeno-associated Virus Vector rAAV/DJ/CAG for Targeted Gene Delivery to Melanoma Cells Metastasized to the Lung

A comprehensive analysis and resource to use CRISPR-Cas13 for broad-spectrum targeting of RNA viruses

A lung tropic AAV vector improves survival in a mouse model of surfactant B deficiency

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