ArticleMolecular therapy : the journal of the American Society of Gene Therapy2009
Cationic lipid formulations alter the in vivo tropism of AAV2/9 vector in lung.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 29 citations in OpenAlex.
- Revolution of AAV in Drug Discovery: From Delivery System to Clinical Application.Journal of medical virology · 2025Review
- Membrane Filtration of Nanoscale Biomaterials: Model System and Membrane Performance Evaluation for AAV2 Viral Vector Clarification and Recovery.Nanomaterials (Basel, Switzerland) · 2025Article
- Adeno-Associated Virus Engineering and Load Strategy for Tropism Modification, Immune Evasion and Enhanced Transgene Expression.International journal of nanomedicine · 2024Review
- Delivering CRISPR to the HIV-1 reservoirs.Frontiers in microbiology · 2024Review
- Development of a Bispecific Antibody-Based Platform for Retargeting of Capsid Modified AAV Vectors.International journal of molecular sciences · 2021Article
- Advances and challenges in adeno-associated viral inner-ear gene therapy for sensorineural hearing loss.Molecular therapy. Methods & clinical development · 2021Review
- Self-complementarity in adeno-associated virus enhances transduction and gene expression in mouse cochlear tissues.PloS one · 2020Article
- Removal of Endotoxin from rAAV Samples Using a Simple Detergent-Based Protocol.Molecular therapy. Methods & clinical development · 2019Article
- Biopolymers augment viral vectors based gene delivery.Journal of biosciences · 2019Review
- Antibacterial activity of the human host defence peptide LL-37 and selected synthetic cationic lipids against bacteria associated with oral and upper respiratory tract infections.The Journal of antimicrobial chemotherapy · 2013Article
- Interaction of 3β-amino-5-cholestene with phospholipids in binary and ternary bilayer membranes.Langmuir : the ACS journal of surfaces and colloids · 2012Article
- A novel polyethyleneimine-coated adeno-associated virus-like particle formulation for efficient siRNA delivery in breast cancer therapy: preparation and in vitro analysis.International journal of nanomedicine · 2012Article
- Article
- AAV's anatomy: roadmap for optimizing vectors for translational success.Current gene therapy · 2010Article
- Combined antibacterial and anti-inflammatory activity of a cationic disubstituted dexamethasone-spermine conjugate.Antimicrobial agents and chemotherapy · 2010Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Physicochemical properties of gene transfer vectors play an important role in both transduction efficiency and biodistribution following airway delivery. Adeno-associated virus (AAV) vectors are currently used in many gene transfer applications; however, the respiratory epithelium remains a challenging target. We synthesized two cationic sterol-based lipids, dexamethasone-spermine (DS) and disubstituted spermine (D(2)S) for pulmonary gene targeting. Scanning and transmission electron micrographs (TEM) confirmed that AAV/lipid formulations produced submicron-sized clusters. When AAV2/9 or AAV2/6.2 were formulated with these cationic lipids, the complexes had positive zeta potential (zeta) and the transduction efficiency in cultured A549 cells increased by sevenfold and sixfold, respectively. Transduction of cultured human airway epithelium with AAV2/6.2-lipid formulations also showed approximately twofold increase in green fluorescence protein (GFP) positive cells as quantified by flow cytometry. Intranasal administration of 10(11) genome copies (GC) of AAV2/9 and AAV2/6.2 coformulated with lipid formulations resulted in an average fourfold increase in transgene expression for both vectors. Formulation of AAV2/9 with DS changed the tropism of this vector for the alveolar epithelium, resulting in successful transduction of conducting airway epithelium. Our results suggest that formulating AAV2/9 and AAV2/6.2 with DS and D(2)S can lead to improved physicochemical characteristics for in vivo gene delivery to lung.
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