Intravenously administered oligonucleotides can be delivered to conducting airway epithelium via the bronchial circulation

Holder, Emma; Griesenbach, Uta; Li, S; Huang, Leaf; Rogers, Duncan F.; Jeffery, Peter K.; Geddes, Duncan M.; Alton, Eric W.F.W.

doi:10.1038/sj.gt.3302811

Cited by 6 publications

(3 citation statements)

References 34 publications

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“…Whether or not this method of administration may result in a therapeutic effect in relevant CF animal models has to be demonstrated. Using the bronchial circulation might be another approach and has already been exploited for gene-therapy vectors [20]. The systemic route would be significant only if the role of alveolar epithelium and macrophages in the pathogenesis of CF lung disease is clarified.…”

Section: Expert Commentarymentioning

confidence: 99%

Stem cell therapy for cystic fibrosis: current status and future prospects

Piro

Rejman

Conese

2008

Expert Review of Respiratory Medicine

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Although cystic fibrosis (CF), an autosomal recessive disease caused by mutations in the gene encoding for the CF transmembrane conductance regulator (CFTR), seems a good candidate for gene therapy, 15 years of intense investigation and a number of clinical trials have not yet produced a viable clinical gene-therapy strategy. In addition, the duration of gene expression has been shown to be limited, only lasting 1-4 weeks. Therefore, alternative approaches involve the search for, and use of, stem cell populations. Bone marrow contains different stem cell types, including hematopoietic stem cells and multipotent mesenchymal stromal cells. Numerous studies have now demonstrated the ability of hematopoietic stem cells and mesenchymal stromal cells to home to the lung and differentiate into epithelial cells of both the conducting airways and the alveolar region. However, engraftment of bone marrow-derived stem cells into the airways is a very inefficient process. Detailed knowledge of the cellular and molecular determinants governing homing to the lung and transformation of marrow cells into lung epithelial cells would benefit this process. Despite a very low level of engraftment of donor cells into the nose and gut, significant CFTR mRNA expression and a measurable level of correction of the electrophysiological defect were observed after transplantation of wild-type marrow cells into CF mice. It is uncertain whether this effect is due to the presence of CFTR-expressing epithelial cells derived from donor cells or to the immunomodulatory role of transplanted cells. Finally, initial studies on the usefulness of umbilical cord blood and embryonic stem cells in the generation of airway epithelial cells will be discussed in this review.

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Section: Expert Commentarymentioning

confidence: 99%

Stem cell therapy for cystic fibrosis: current status and future prospects

Piro

Rejman

Conese

2008

Expert Review of Respiratory Medicine

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“…This information, together with our present knowledge of protamine structure and function and advances in transgene technology, make it possible to test directly how specific changes in protamine structure (for example, the removal of phosphorylation sites, changes in P2 processing sites or removal of functional thiols and zinc-coordinating residues) and sperm chromatin composition impact on protamine function, chromatin packaging, male fertility and the progression of early embryogenesis. We have also learned enough about how protamine functions to create small synthetic DNA-binding proteins or peptides for use in packaging, protecting and aiding the delivery of functional genes to selected cell populations for use in gene therapy [ 76 - 78 ], gene silencing [ 79 ] or in targeting toxic genes to tumor cells [ 80 ]. The self-assembling nature of the protamine-DNA complex may also provide a new approach that can be used to create nanometer- to micrometer-scale self-assembling electrically conductive polymers for use in constructing biocompatible electrical circuits.…”

Section: Frontiersmentioning

confidence: 99%

The protamine family of sperm nuclear proteins

2007

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SummaryThe protamines are a diverse family of small arginine-rich proteins that are synthesized in the late-stage spermatids of many animals and plants and bind to DNA, condensing the spermatid genome into a genetically inactive state. Vertebrates have from one to 15 protamine genes per haploid genome, which are clustered together on the same chromosome. Comparison of protamine gene and amino-acid sequences suggests that the family evolved from specialized histones through protamine-like proteins to the true protamines. Structural elements present in all true protamines are a series of arginine-rich DNA-anchoring domains (often containing a mixture of arginine and lysine residues in non-mammalian protamines) and multiple phosphorylation sites. The two protamines found in mammals, P1 and P2, are the most widely studied. P1 packages sperm DNA in all mammals, whereas protamine P2 is present only in the sperm of primates, many rodents and a subset of other placental mammals. P2, but not P1, is synthesized as a precursor that undergoes proteolytic processing after binding to DNA and also binds a zinc atom, the function of which is not known. P1 and P2 are phosphorylated soon after their synthesis, but after binding to DNA most of the phosphate groups are removed and cysteine residues are oxidized, forming disulfide bridges that link the protamines together. Both P1 and P2 have been shown to be required for normal sperm function in primates and many rodents.

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“…Due to the high affinity to DNA backbone, the positivecharged PRMs, especially PRM1, is found to be great help in facilitating the development of novel gene carriers to selected cell populations (25)(26)(27)(28)(86)(87)(88). Lately, Weide et al developed a more feasible and safe method to deliver tumor vaccine.…”

Section: Novel Vector For Drug Delivery Systemmentioning

confidence: 99%

The expression, function, and utilization of Protamine1: a literature review

Ren¹,

Chen²,

Tian³

et al. 2021

Transl Cancer Res TCR

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Objective Protamine 1 (PRM1) is specific in sperm and plays essential roles in fertilization, also a member of cancer testis antigen (CTA) family. This study aims to summarize the expression and function of PRM1 in spermatogenesis, and to broaden the current knowledge and inspire future development of PRM1-based therapeutic strategies in cancer treatment and nanomedicine. Background The protamine proteins, are characterized by an arginine-rich core and cysteine residues. Humans express two types of protamine: PRM1 and PRM2. The abnormal expression or proportion of PRM1 and PRM2 is known to be associated with subfertility and infertility, especially for PRM1 which is highly evolutionary conserved in mammalians and expressed in all vertebrates. Biological functions of PRM1 have been unveiled in diverse cellular processes, such as tumorigenesis, somatic cell nucleus transfer, and drug delivery systems. Moreover, PRM1 is identified as a CTA in chronic leukemia (CLL) and colorectal cancer (CRC). Methods Literature was obtained using PubMed and the keywords protamine 1, PRM1, or P1, from January 1, 1980, through July 20, 2021. We also collect the additional evidence through screening references of articles identified through the PubMed searches. Conclusions PRM1 is well-studied in male infertility, and further researches and attempts to develop PRM1 as novel tumor marker, as well as drug delivery vector, will be of important clinical significance.

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Intravenously administered oligonucleotides can be delivered to conducting airway epithelium via the bronchial circulation

Cited by 6 publications

References 34 publications

Stem cell therapy for cystic fibrosis: current status and future prospects

Stem cell therapy for cystic fibrosis: current status and future prospects

The protamine family of sperm nuclear proteins

The expression, function, and utilization of Protamine1: a literature review

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