Cftr gene sendai virus. Medical search. Frequent questions

PURPOSE OF REVIEW: Advances in cystic fibrosis (CF) therapies over the past decade pivotally changed the morbidity and mortality of CF with the advent of cystic fibrosis transmembrane conductance regulator (CFTR) modulators that rescue dysfunctional CFTR protein in individuals with eligible genotypes. (bvsalud.org)
The prospect of gene therapy for inherited and acquired respiratory disease has energized the research community since the 1980s, with cystic fibrosis, as a monogenic disorder, driving early efforts to develop effective strategies. (bvsalud.org)
We have recently shown that non-viral gene therapy can stabilise the decline of lung function in patients with cystic fibrosis (CF). However, the effect was modest, and more potent gene transfer agents are still required. (bvsalud.org)
cystic fibrosis transmembrane conductance receptor (CFTR) expression and function were assessed in CF models using this lead candidate vector. (bvsalud.org)

These historic and timely developments are of significant relevance for advancing genetic therapies in CF. RECENT FINDINGS: This article reviews the main themes of semi-permanent genetic therapy strategies covering recent literature focused on: adenovirus and adeno-associated virus vector delivery, advances in lentivirus vector use and safety considerations, mRNA delivery and antisense oligonucleotide drug development. (bvsalud.org)

Lentiviral (LV) vectors of the Retroviridae family show interesting properties for monogenic gene therapy, since they integrate into the host genome and allow long-lasting gene expression 22 . (nature.com)
Overprinting has been hypothesized as a mechanism for de novo emergence of new genes from existing sequences, either older genes or previously non-coding regions of the genome. (wikipedia.org)
A study on the hepatitis B virus (HBV), whose DNA genome contains numerous overlapping genes, showed the mean number of synonymous nucleotide substitutions per site in overlapping coding regions was significantly lower than that of non-overlapping regions. (wikipedia.org)

Fuson protein (F)/Hemagglutinin/Neuraminidase protein (HN)-pseudotyped lentiviral vectors are more efficient for lung gene transfer than non-viral vectors in preclinical models. (bvsalud.org)

In prokaryotes and viruses overlap must be between coding sequences but not mRNA transcripts, and is defined when these coding sequences share a nucleotide on either the same or opposite strands. (wikipedia.org)
In eukaryotes, gene overlap is almost always defined as mRNA transcript overlap. (wikipedia.org)
Specifically, a gene overlap in eukaryotes is defined when at least one nucleotide is shared between the boundaries of the primary mRNA transcripts of two or more genes, such that a DNA base mutation at any point of the overlapping region would affect the transcripts of all genes involved. (wikipedia.org)

Gene therapy has been utilized successfully to repair or inactivate mutations in animal models of monogenic human diseases 19 as well as human in vitro cells 12 . (nature.com)
DNA and RNA based therapies) in CF are informed by historic challenges of CF gene therapy trials, recent FDA guidance informed by non-CF gene therapy trials, and advances in therapeutic applications related to severe acute respiratory syndrome coronavirus 2 vaccine development. (bvsalud.org)
The fact that there are still no approved gene therapy products for the lung, despite many early phase clinical trials, illustrates the scale of the challenge: In the 1990s, first-generation non-viral and viral vector systems demonstrated proof-of-concept but low efficacy. (bvsalud.org)
Nature Gene Therapy, 23 (12). (testavec.com)
Themis, M. (2012) ' Monitoring for potential adverse effects of prenatal gene therapy: Genotoxicity analysis in vitro and on small animal models ex vivo and in vivo '.Methods in Molecular Biology, 891. (testavec.com)
Human Gene Therapy, 17 (7). (testavec.com)

Overprinted genes are particularly common features of the genomic organization of viruses, likely to greatly increase the number of potential expressible genes from a small set of viral genetic information. (wikipedia.org)
Early approaches were based on gene addition, where a new DNA copy of a gene is introduced to complement a genetic mutation: however, the advent of RNA-based products that can directly express a therapeutic protein or manipulate gene expression, together with the expanding range of tools for gene editing, has stimulated the development of alternative approaches. (bvsalud.org)

We alter the deficiency by infecting the SFTPB deficient iPSCs with a lentivirus carrying the wild type SFTPB gene. (nature.com)

However, a significant proportion of the CF population is in need of alternative treatment strategies to address CFTR variants that are ineligible for therapeutic protein correction and/or potentiation. (bvsalud.org)

murine leukemia virus in clinical trials. (what-when-how.com)

Overlapping genes can also be classified by phases, which describe their relative reading frames: In-phase overlap occurs when the shared sequences use the same reading frame. (wikipedia.org)

The alternative open reading frames (ORF) are thought to be created by critical nucleotide substitutions within an expressible pre-existing gene, which can be induced to express a novel protein while still preserving the function of the original gene. (wikipedia.org)
duce a specific protein, usually due to a single defective gene. (what-when-how.com)

In this way, a nucleotide sequence may make a contribution to the function of one or more gene products. (wikipedia.org)
Overlapping genes are reasoned to evolve under strict constraints as a single nucleotide substitution is able to alter the structure and function of the two proteins simultaneously. (wikipedia.org)

Subsequently, overprinting is also believed to be a source of novel proteins, as de novo proteins coded by these novel genes usually lack remote homologs in databases. (wikipedia.org)
It is likely that overprinting is responsible for the generation of numerous novel proteins by viruses over the course of their evolutionary history. (wikipedia.org)
In one model, the two proteins encoded by their respective overlapping genes evolve under similar selection pressures. (wikipedia.org)

Unidirectional genes with phase 0 overlap are not considered distinct genes, but rather as alternative start sites of the same gene. (wikipedia.org)

16. Restoration of cyclic adenosine monophosphate-stimulated chloride channel activity in human cystic fibrosis tracheobronchial submucosal gland cells by adenovirus-mediated and cationic lipid-mediated gene transfer. (nih.gov)
19. Adenovirus-mediated gene transfer for cystic fibrosis: quantitative evaluation of repeated in vivo vector administration to the lung. (nih.gov)
Correction by adenovirus-mediated CFTR gene transfer. (nih.gov)
Two studies have shown that adenovirus-mediated CFTR expression or virus-induced inflammatory responses may, to a degree, protect CF mice from the effects of bacteria-induced lung inflammation. (medscape.com)
[ 24 , 25 ] Importantly, two studies recently disproved the suggestion that transient adenovirus-mediated CFTR expression in utero prolonged the survival of CF-knockout mice. (medscape.com)

Sendai virus-mediated CFTR gene transfer to the airway epithelium. (ox.ac.uk)
In addition, when compared to a SeV control vector, a higher degree of inflammation and epithelial damage was found in the nasal epithelium of mice treated with SeV-CFTR. (ox.ac.uk)
17. Cationic lipids for reporter gene and CFTR transfer to rat pulmonary epithelium. (nih.gov)

We have shown that recombinant Sendai virus (SeV) is highly efficient in mediating gene transfer to differentiated airway epithelial cells, because of its capacity to overcome the intra- and extracellular barriers known to limit gene delivery. (ox.ac.uk)
identified a recombinant AAV virus that transduced organotypic human lung cultures 100-fold better than parental strains, although the performance of this novel virus in the human lung remains to be established. (medscape.com)

5. Uptake of plasmid/glycosylated polymer complexes and gene transfer efficiency in differentiated airway epithelial cells. (nih.gov)

Second-generation transmission-incompetent F-deleted SeV-CFTR led to similar correction of the CF chloride transport defect in vivo as first-generation transmission-competent vectors. (ox.ac.uk)
18. Efficient CFTR expression from AAV vectors packaged with promoters--the second generation. (nih.gov)
[ 22 ] Helper-dependent ('gutted') adenoviral vectors, which are depleted of all viral genes, may be less immunostimulatory and have improved safety profiles compared with first- and second-generation viruses, which only have a subset of viral genes deleted, [ 23 ] but do not currently prevent the induction of immune responses. (medscape.com)
[ 26 , 27 ] Overall, the use of adenoviral vectors for preclinical CF gene therapy has drastically decreased over the last 5 years, and the use of adenoviral vectors will be restricted to preclinical proof-of-principle studies until the problems of repeat administration can be overcome. (medscape.com)

Overlapping genes are present in and a fundamental feature of both cellular and viral genomes. (wikipedia.org)
Overprinted genes are particularly common features of the genomic organization of viruses, likely to greatly increase the number of potential expressible genes from a small set of viral genetic information. (wikipedia.org)
The Identification8-fLuc cell range was transducted from the Lab of Molecular Virology and Gene Therapy and Leuven Viral Vector Primary inside our institute. (baxkyardgardener.com)

Transposons are called "Jumping genes", and are examples of mobile genetic elements. (aplustopper.com)

The set represents ~36,000 full length genes and EST clusters derived from sequence clusters in Build 74 of the Mouse Unigene Database. (nih.gov)
An overlapping gene (or OLG) is a gene whose expressible nucleotide sequence partially overlaps with the expressible nucleotide sequence of another gene. (wikipedia.org)
In this way, a nucleotide sequence may make a contribution to the function of one or more gene products. (wikipedia.org)
Overprinting refers to a type of overlap in which all or part of the sequence of one gene is read in an alternate reading frame from another gene at the same locus. (wikipedia.org)

9. Single-dose lentiviral gene transfer for lifetime airway gene expression. (nih.gov)
iii) Jacob and Monod proposed the Operon concept of Gene Expression in bacteria. (aplustopper.com)

Strategies to overcome the AAV packaging problem, thereby allowing the incorporation of stronger promoters in addition to the large CFTR gene, have been developed, including approaches based on trans -splicing [ 32 ] and homologous recombination. (medscape.com)

8. Targeting of cell receptors and gene transfer efficiency: a balancing act. (nih.gov)
One would speculate that both of these strategies would lead to reduced transfection efficiency when compared with the administration of one intact virus to the lung. (medscape.com)

More recently, AAV2 genomes with capsids from serotypes 1, 5, 6 and 9 have been evaluated for lung gene therapy, and appear to be more efficient in transducing AECs than AAV2. (medscape.com)

6. Efficient gene transfer by histidylated polylysine/pDNA complexes. (nih.gov)

In prokaryotes and viruses overlap must be between coding sequences but not mRNA transcripts, and is defined when these coding sequences share a nucleotide on either the same or opposite strands. (wikipedia.org)
Overlapping genes can also be classified by phases, which describe their relative reading frames: In-phase overlap occurs when the shared sequences use the same reading frame. (wikipedia.org)

[ 33 ] The basic principle of these techniques is to split the therapeutic cDNA and required promoter elements and package them into two viruses, which when transfecting the same cell may recombine and generate a full-length therapeutic gene. (medscape.com)

In one model, the two proteins encoded by their respective overlapping genes evolve under similar selection pressures. (wikipedia.org)

Following in vitro transduction with SeV-CFTR, a chloride-selective current was observed using whole-cell and single-channel patch-clamp techniques. (ox.ac.uk)

Specifically, a gene overlap in eukaryotes is defined when at least one nucleotide is shared between the boundaries of the primary mRNA transcripts of two or more genes, such that a DNA base mutation at any point of the overlapping region would affect the transcripts of all genes involved. (wikipedia.org)

Studies on overlapping genes suggest that their evolution can be summarized in two possible models. (wikipedia.org)

The current definition of an overlapping gene varies significantly between eukaryotes, prokaryotes, and viruses. (wikipedia.org)

13. Serum albumin enhances polyethylenimine-mediated gene delivery to human respiratory epithelial cells. (nih.gov)

Vesicular stomatitis virus (VSV) and herpes simplex virus type 1 (HSV-1) infection induced a higher level of IFN-ß protein in NOG1 deficient mice. (bvsalud.org)

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