Recombinant adenovirus (Ad) vectors are being considered for in vivo delivery of various therapeutic genes. One limiting factor in the development of Ad-based gene therapy is the low efficiency of gene transfer to target tissues such as vascular endothelium, smooth muscle, and airway epithelium. Complexing Ad vector with various polycations has been shown to enhance transduction of cell lines otherwise resistant to Ad infection in vitro. On the basis of this observation, the activity of Ad/polycation complexes was tested in vivo in the mouse lung. The results indicated that several polycations were capable of enhancing transduction of mouse respiratory epithelium, leading to a 1-2 log increase in levels of transgene expression. Poly-L-lysine (PLL) and DEAE-dextran were examined further and were found to increase Ad-mediated gene transfer without any additional toxicity as assessed histologically or through the measurement of inflammatory cytokines in bronchoalveolar lavages. The two polycations also failed to affect the humoral response against Ad vector and were themselves nonimmunogenic under conditions leading to enhanced gene transfer. Moreover, the ability to use reduced doses of vector complexed with polycations resulted in lower levels of Ad-specific antibodies and, thereby, improved readministration of vector. These results suggest that complexing Ad vectors with polycations has the potential to improve the therapeutic index by increasing transgene expression while reducing unwanted responses associated with high doses of vector.

Download full-text PDF

Source
http://dx.doi.org/10.1089/hum.1998.9.10-1469DOI Listing

Publication Analysis

Top Keywords

gene transfer
16
mouse lung
8
vector polycations
8
transgene expression
8
doses vector
8
vector
6
polycations
6
potentiation gene
4
transfer
4
transfer mouse
4

Similar Publications

One strategy for CO mitigation is using photosynthetic microorganisms to sequester CO under high concentrations, such as in flue gases. While elevated CO levels generally promote growth, excessively high levels inhibit growth through uncertain mechanisms. This study investigated the physiology of the cyanobacterium Synechocystis sp.

View Article and Find Full Text PDF

Some key secondary metabolism genes are important for driving the infection process of entomopathogenic fungi; however, their chemical substance basis has not been well investigated. Here, mixtures of polyol lipids are discovered, which are synthesized through iterative chain transfer-esterification-hydrolysis cycles catalyzed by serine hydrolase during the release of online highly reducing polyketide intermediates. Importantly, an gene knockout experiment revealed that the synthesis of polyol lipids is necessary for rodlet layer formation on the cell wall of .

View Article and Find Full Text PDF

A plasmid with the gene enhances the fitness of strains under laboratory conditions.

Microbiology (Reading)

January 2025

Instituto de Microbiologa, Colegio de Ciencias Biolgicas y Ambientales, Universidad San Francisco de Quito, Quito, Ecuador.

Antimicrobial resistance (AMR) is a major threat to global public health that continues to grow owing to selective pressure caused by the use and overuse of antimicrobial drugs. Resistance spread by plasmids is of special concern, as they can mediate a wide distribution of AMR genes, including those encoding extended-spectrum -lactamases (ESBLs). The CTX-M family of ESBLs has rapidly spread worldwide, playing a large role in the declining effectiveness of third-generation cephalosporins.

View Article and Find Full Text PDF

Plant mitochondrial genomes (mitogenomes) experience remarkable levels of horizontal gene transfer (HGT), including the recent discovery that orchids anciently acquired DNA from fungal mitogenomes. Thus far, however, there is no evidence that any of the genes from this interkingdom HGT are functional in orchid mitogenomes. Here, we applied a specialized sequencing approach to the orchid Corallorhiza maculata and found that some fungal-derived tRNA genes in the transferred region are transcribed, post-transcriptionally modified, and aminoacylated.

View Article and Find Full Text PDF

Mitochondrial genomes are a rich source of data for various downstream analyses such as population genetics, phylogeny, and systematics. Today it is possible to assemble rapidly large numbers of mitogenomes, mainly employing next-generation sequencing and third-generation sequencing. However, verification of the correctness of the generated sequences is often lacking, especially for noncoding, length-variable parts.

View Article and Find Full Text PDF

Want 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!