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1.
Sci Rep ; 11(1): 15694, 2021 08 03.
Article in English | MEDLINE | ID: mdl-34344952

ABSTRACT

Respiratory syncytial virus (RSV) infection is a common cause of hospitalisation in infants and the elderly. Palivizumab prophylaxis is the only approved treatment modality but is costly and only offered to select vulnerable populations. Here, we investigated gene delivery approaches via recombinant adeno-associated virus (rAAV2/8) and simian immunodeficiency virus (rSIV.F/HN) vectors to achieve sustained in vivo production of palivizumab in a murine model. Delivery of palivizumab-expressing vectors 28 days prior to RSV challenge resulted in complete protection from RSV-induced weight loss. This approach offers prophylaxis against RSV infection, allowing for wider use and reduction in treatment costs in vulnerable populations.


Subject(s)
Antibodies, Monoclonal, Humanized/genetics , Gene Expression , Genetic Therapy , Palivizumab/genetics , Respiratory Syncytial Virus Infections/therapy , Respiratory Syncytial Virus Infections/virology , Respiratory Syncytial Viruses , Animals , Dependovirus/genetics , Disease Models, Animal , Female , Gene Transfer Techniques , Genetic Engineering , Genetic Vectors/administration & dosage , Genetic Vectors/genetics , Injections, Intramuscular , Lentivirus/genetics , Mice , Respiratory Syncytial Virus Infections/immunology , Respiratory Syncytial Viruses/immunology , Transduction, Genetic , Treatment Outcome
2.
PLoS One ; 11(6): e0157605, 2016.
Article in English | MEDLINE | ID: mdl-27304457

ABSTRACT

Integrons are genetic elements capable of capturing and expressing open reading frames (ORFs) embedded within gene cassettes. They are involved in the dissemination of antibiotic resistance genes (ARGs) in clinically important pathogens. Although the ARGs are common in the oral cavity the association of integrons and antibiotic resistance has not been reported there. In this work, a PCR-based approach was used to investigate the presence of integrons and associated gene cassettes in human oral metagenomic DNA obtained from both the UK and Bangladesh. We identified a diverse array of gene cassettes containing ORFs predicted to confer antimicrobial resistance and other adaptive traits. The predicted proteins include a putative streptogramin A O-acetyltransferase, a bleomycin binding protein, cof-like hydrolase, competence and motility related proteins. This is the first study detecting integron gene cassettes directly from oral metagenomic DNA samples. The predicted proteins are likely to carry out a multitude of functions; however, the function of the majority is yet unknown.


Subject(s)
Integrons/genetics , Metagenome/genetics , Microbiota/genetics , Saliva/microbiology , Adult , Aged , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , Bangladesh , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , Drug Resistance, Microbial/drug effects , Drug Resistance, Microbial/genetics , Female , Genes, Bacterial/genetics , Humans , Male , Middle Aged , Open Reading Frames/genetics , Polymerase Chain Reaction , Sequence Analysis, DNA , United Kingdom , Young Adult
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