AI Article Synopsis
Article Abstract
Adeno-associated virus (AAV)-mediated gene delivery holds great promise for gene therapy. However, the non-invasive delivery of AAV for lung tissues has not been adequately established. Here, we revealed that the intratracheal administration of an appropriate amount of AAV2/8 predominantly targets lung tissue. AAV-mediated gene delivery that we used in this study induced the expression of the desired protein in lung parenchymal cells, including alveolar type II cells. We harnessed the technique to develop severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-susceptible mice. Three kinds of immune function-relevant gene knockout (KO) mice were transduced with AAV encoding human angiotensin-converting enzyme 2 (hACE2) and then injected with SARS-CoV-2. Among these mice, type I interferon receptor (IFNAR) KO mice showed increased viral titer in the lungs compared to that in the other KO mice. Moreover, nucleocapsid protein of SARS-CoV-2 and multiple lesions in the trachea and lung were observed in AAV-hACE2-transduced, SARS-CoV-2-infected IFNAR KO mice, indicating the involvement of type I interferon signaling in the protection of SARS-CoV-2. In this study, we demonstrate the ease and rapidness of the intratracheal administration of AAV for targeting lung tissue in mice, and this can be used to study diverse pulmonary diseases.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8739362 | PMC |
| http://dx.doi.org/10.1016/j.ymthe.2022.01.010 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Durable lymphocyte subset elimination upon a single dose of AAV-delivered depletion antibody dissects immune control of chronic viral infection.
Immunity
December 2024
Department of Biomedicine, University of Basel, 4009 Basel, Switzerland. Electronic address:
To interrogate the role of specific immune cells in infection, cancer, and autoimmunity, immunologists commonly use monoclonal depletion antibodies (depletion-mAbs) or genetically engineered mouse models (GEMMs). To generate a tool that combines specific advantages and avoids select drawbacks of the two methods, we engineered adeno-associated viral vectors expressing depletion mAbs (depletion-AAVs). Single-dose depletion-AAV administration durably eliminated lymphocyte subsets in mice and avoided accessory deficiencies of GEMMs, such as marginal zone defects in B cell-deficient animals.
View Article and Find Full Text PDFComparative assessment of the transduction efficiency and safety associated with the delivery of AAV9-GFP vector via lumbar puncture to cynomolgus macaques with and without anti-AAV9 pre-existing antibodies.
Mol Ther Methods Clin Dev
December 2024
Preclinical Safety (PCS), Novartis Biomedical Research, Cambridge, MA, USA.
Administration of AAV-based gene therapies into the intra-cerebrospinal fluid (CSF) compartments via routes such as lumbar puncture (LP) has been implemented as an alternative to intravenous dosing to target the CNS regions. This route enables lower doses, decreases systemic toxicity, and circumvents intravascular pre-existing anti-AAV antibodies. In this study, AAV9-GFP vectors were administered via LP to juvenile cynomolgus macaques with and without pre-existing serum anti-AAV9 antibodies at a 5.
View Article and Find Full Text PDFCurrent and Emerging Issues in Adeno-Associated Virus Vector-Mediated Liver-Directed Gene Therapy.
Hum Gene Ther
December 2024
Telethon Institute of Genetics and Medicine, Pozzuoli, Italy.
Adeno-associated virus (AAV) vectors have demonstrated safety and efficacy for gene transfer to hepatocytes in preclinical models, in various clinical trials and from a clinical experience with a growing number of approved gene therapy products. Although the exact duration is unknown, the expression of therapeutic genes in hepatocytes remains stable for several years after a single administration of the vector at clinically relevant doses in adult patients with hemophilia and other inherited metabolic disorders. However, clinical applications, especially for diseases requiring high AAV vector doses by intravenous administrations, have raised several concerns.
View Article and Find Full Text PDFThe vectors went in two-by-two: Transduction efficiency and tolerability of dual and triple rAAV vector delivery following intravitreal injection for genome-editing applications.
Exp Eye Res
December 2024
Department of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, WI, 53226, USA; Department of Ophthalmology & Visual Sciences, Medical College of Wisconsin, WI, 53226, USA. Electronic address:
Genome or prime editing has become a promising tool for the treatment of hereditary disorders affecting the inner retina, such as dominant optic neuropathies. In vivo delivery of gene editors, such as Cas9, is typically achieved using recombinant adeno-associated virus (rAAV) vectors, which have a broad range of cellular tropisms and are well tolerated following intravitreal administration. Owing to the large size of gene editing constructs and the limited carrying capacity of rAAV (<5.
View Article and Find Full Text PDFOcular toxicity, distribution, and shedding of intravitreal AAV-eqIL-10 in horses.
Mol Ther Methods Clin Dev
December 2024
Clinical Sciences, North Carolina State University, Raleigh, NC 27607, USA.
Non-infectious uveitis (NIU) is a painful recurrent disease affecting 2%-5% of horses. Current treatments require frequent administration with associated adverse events. In a previous study, intravitreal (IVT) adeno-associated virus (AAV) harboring equine interleukin-10 (eqIL-10) cDNA inhibited experimental uveitis in rats.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!