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Advanced Healthcare Materials Oct 2018In the beginning of the 21st century, therapeutic oligonucleotides have shown great potential for the treatment of many life-threatening diseases. However, effective... (Review)
Review
In the beginning of the 21st century, therapeutic oligonucleotides have shown great potential for the treatment of many life-threatening diseases. However, effective delivery of therapeutic oligonucleotides to the targeted location in vivo remains a major issue. As an emerging field, DNA nanotechnology is applied in many aspects including bioimaging, biosensing, and drug delivery. With sequence programming and optimization, a series of DNA nanostructures can be precisely engineered with defined size, shape, surface chemistry, and function. Simply with hybridization, therapeutic oligonucleotides including unmethylated cytosine-phosphate-guanine dinucleotide oligos, small interfering RNA (siRNA) or antisense RNA, single guide RNA of the regularly interspaced short palindromic repeat-Cas9 system, and aptamers, are successfully loaded on DNA nanostructures for delivery. In this progress report, the development history of DNA nanotechnology is first introduced, and then the mechanisms and means for cellular uptake of DNA nanostructures are discussed. Next, current approaches to deliver therapeutic oligonucleotides with DNA nanovehicles are summarized. In the end, the challenges and opportunities for DNA nanostructure-based systems for the delivery of therapeutic oligonucleotides are discussed.
Topics: Animals; CRISPR-Associated Protein 9; DNA; Humans; Interspersed Repetitive Sequences; Inverted Repeat Sequences; Mice; Nanostructures; Nanotechnology; Oligonucleotides; RNA, Antisense
PubMed: 29356400
DOI: 10.1002/adhm.201701153 -
Current Opinion in Genetics &... Dec 2003Mobile elements make up large portions of most eukaryotic genomes. They create genetic instability, not only through insertional mutation but also by contributing... (Review)
Review
Mobile elements make up large portions of most eukaryotic genomes. They create genetic instability, not only through insertional mutation but also by contributing recombination substrates, both during and long after their insertion. The combination of whole-genome sequences and the development of innovative new assays to test the function of mobile elements have increased our understanding of how these elements mobilize and how their insertion impacts genome diversity and human disease.
Topics: Animals; Eukaryotic Cells; Evolution, Molecular; Genetic Variation; Genome; Genomic Instability; Humans; Interspersed Repetitive Sequences; Mammals; Retroelements; Sequence Analysis, DNA
PubMed: 14638329
DOI: 10.1016/j.gde.2003.10.013 -
Nature Structural Biology Apr 2001
Topics: Animals; DNA Transposable Elements; Genetics; History, 20th Century; Humans; Interspersed Repetitive Sequences; Mutagenesis; Zea mays
PubMed: 11276245
DOI: 10.1038/86161 -
Philosophical Transactions of the Royal... Aug 2016The history of life is punctuated by evolutionary transitions which engender emergence of new levels of biological organization that involves selection acting at... (Review)
Review
The history of life is punctuated by evolutionary transitions which engender emergence of new levels of biological organization that involves selection acting at increasingly complex ensembles of biological entities. Major evolutionary transitions include the origin of prokaryotic and then eukaryotic cells, multicellular organisms and eusocial animals. All or nearly all cellular life forms are hosts to diverse selfish genetic elements with various levels of autonomy including plasmids, transposons and viruses. I present evidence that, at least up to and including the origin of multicellularity, evolutionary transitions are driven by the coevolution of hosts with these genetic parasites along with sharing of 'public goods'. Selfish elements drive evolutionary transitions at two distinct levels. First, mathematical modelling of evolutionary processes, such as evolution of primitive replicator populations or unicellular organisms, indicates that only increasing organizational complexity, e.g. emergence of multicellular aggregates, can prevent the collapse of the host-parasite system under the pressure of parasites. Second, comparative genomic analysis reveals numerous cases of recruitment of genes with essential functions in cellular life forms, including those that enable evolutionary transitions.This article is part of the themed issue 'The major synthetic evolutionary transitions'.
Topics: Biological Evolution; Interspersed Repetitive Sequences; Viruses
PubMed: 27431520
DOI: 10.1098/rstb.2015.0442 -
Annual Review of Microbiology Sep 2023Mobile genetic elements are key to the evolution of bacteria and traits that affect host and ecosystem health. Here, we use a framework of a hierarchical and modular... (Review)
Review
Mobile genetic elements are key to the evolution of bacteria and traits that affect host and ecosystem health. Here, we use a framework of a hierarchical and modular system that scales from genes to populations to synthesize recent findings on mobile genetic elements (MGEs) of bacteria. Doing so highlights the role that emergent properties of flexibility, robustness, and genetic capacitance of MGEs have on the evolution of bacteria. Some of their traits can be stored, shared, and diversified across different MGEs, taxa of bacteria, and time. Collectively, these properties contribute to maintaining functionality against perturbations while allowing changes to accumulate in order to diversify and give rise to new traits. These properties of MGEs have long challenged our abilities to study them. Implementation of new technologies and strategies allows for MGEs to be analyzed in new and powerful ways.
Topics: Ecosystem; Bacteria; Phenotype; Interspersed Repetitive Sequences
PubMed: 37437216
DOI: 10.1146/annurev-micro-032521-022006 -
BioEssays : News and Reviews in... Feb 2023Integrative mobile genetic elements (MGEs), such as transposons and insertion sequences, propagate within bacterial genomes, but persistence times in individual lineages...
Integrative mobile genetic elements (MGEs), such as transposons and insertion sequences, propagate within bacterial genomes, but persistence times in individual lineages are short. For long-term survival, MGEs must continuously invade new hosts by horizontal transfer. Theoretically, MGEs that persist for millions of years in single lineages, and are thus subject to vertical inheritance, should not exist. Here we draw attention to an exception - a class of MGE termed REPIN. REPINs are non-autonomous MGEs whose duplication depends on non-jumping RAYT transposases. Comparisons of REPINs and typical MGEs show that replication rates of REPINs are orders of magnitude lower, REPIN population size fluctuations correlate with changes in available genome space, REPIN conservation depends on RAYT function, and REPIN diversity accumulates within host lineages. These data lead to the hypothesis that REPINs form enduring, beneficial associations with eubacterial chromosomes. Given replicative nesting, our hypothesis predicts conflicts arising from the diverging effects of selection acting simultaneously on REPINs and host genomes. Evidence in support comes from patterns of REPIN abundance and diversity in two distantly related bacterial species. Together this bolsters the conclusion that REPINs are the genetic counterpart of mutualistic endosymbiotic bacteria.
Topics: Bacteria; DNA Transposable Elements; Genome, Bacterial; Interspersed Repetitive Sequences
PubMed: 36456469
DOI: 10.1002/bies.202200085 -
Nucleic Acids Research Aug 2021Mobile genetic elements have been harnessed for gene transfer for a wide variety of applications including generation of stable cell lines, recombinant protein...
Mobile genetic elements have been harnessed for gene transfer for a wide variety of applications including generation of stable cell lines, recombinant protein production, creation of transgenic animals, and engineering cell and gene therapy products. The piggyBac transposon family includes transposase or transposase-like proteins from a variety of species including insect, bat and human. Recently, human piggyBac transposable element derived 5 (PGBD5) protein was reported to be able to transpose piggyBac transposons in human cells raising possible safety concerns for piggyBac-mediated gene transfer applications. We evaluated three piggyBac-like proteins across species including piggyBac (insect), piggyBat (bat) and PGBD5 (human) for their ability to mobilize piggyBac transposons in human cells. We observed a lack of cross-species transposition activity. piggyBac and piggyBat activity was restricted to their cognate transposons. PGBD5 was unable to mobilize piggyBac transposons based on excision, colony count and plasmid rescue analysis, and it was unable to bind piggyBac terminal repeats. Within the piggyBac family, we observed a lack of cross-species activity and found that PGBD5 was unable to bind, excise or integrate piggyBac transposons in human cells. Transposition activity appears restricted within species within the piggyBac family of mobile genetic elements.
Topics: Animals; Cell Line; DNA Transposable Elements; Genetic Vectors; Humans; Interspersed Repetitive Sequences; Mutagenesis, Insertional; Plasmids; Transcription Factors; Transposases
PubMed: 34232995
DOI: 10.1093/nar/gkab578 -
Current Genetics Aug 2021Transposable elements (TEs) are ubiquitous mobile genetic elements that hold both disruptive and adaptive potential for species. It has long been postulated that their... (Review)
Review
Transposable elements (TEs) are ubiquitous mobile genetic elements that hold both disruptive and adaptive potential for species. It has long been postulated that their activity may be triggered by hybridization, a hypothesis that received mixed support from studies in various species. While host defense mechanisms against TEs are being elucidated, the increasing volume of genomic data and bioinformatic tools specialized in TE detection enable in-depth characterization of TEs at the levels of species and populations. Here, I borrow elements from the genome ecology theory to illustrate how knowledge of the diversity of TEs and host defense mechanisms may help predict the activity of TEs in the face of hybridization, and how current limitations make this task especially challenging.
Topics: DNA Transposable Elements; Evolution, Molecular; Genome; Genomics; Hybridization, Genetic; Interspersed Repetitive Sequences
PubMed: 33738571
DOI: 10.1007/s00294-021-01169-0 -
Trends in Genetics : TIG May 2013Mobile elements comprise more than half of the human genome, but until recently their large-scale detection was time consuming and challenging. With the development of... (Review)
Review
Mobile elements comprise more than half of the human genome, but until recently their large-scale detection was time consuming and challenging. With the development of new high-throughput sequencing (HTS) technologies, the complete spectrum of mobile element variation in humans can now be identified and analyzed. Thousands of new mobile element insertions (MEIs) have been discovered, yielding new insights into mobile element biology, evolution, and genomic variation. Here, we review several high-throughput methods, with an emphasis on techniques that specifically target MEIs in humans. We highlight recent applications of these methods in evolutionary studies and in the analysis of somatic alterations in human normal and tumor tissues.
Topics: Computational Biology; Genetic Variation; Genome, Human; High-Throughput Nucleotide Sequencing; Humans; Interspersed Repetitive Sequences; Neoplasms
PubMed: 23312846
DOI: 10.1016/j.tig.2012.12.002 -
Environmental Microbiology Apr 2024Horizontal gene transfer (HGT) is a fundamental process in prokaryotic evolution, contributing significantly to diversification and adaptation. HGT is typically...
Horizontal gene transfer (HGT) is a fundamental process in prokaryotic evolution, contributing significantly to diversification and adaptation. HGT is typically facilitated by mobile genetic elements (MGEs), such as conjugative plasmids and phages, which often impose fitness costs on their hosts. However, a considerable number of bacterial genes are involved in defence mechanisms that limit the propagation of MGEs, suggesting they may actively restrict HGT. In our study, we investigated whether defence systems limit HGT by examining the relationship between the HGT rate and the presence of 73 defence systems across 12 bacterial species. We discovered that only six defence systems, three of which were different CRISPR-Cas subtypes, were associated with a reduced gene gain rate at the species evolution scale. Hosts of these defence systems tend to have a smaller pangenome size and fewer phage-related genes compared to genomes without these systems. This suggests that these defence mechanisms inhibit HGT by limiting prophage integration. We hypothesize that the restriction of HGT by defence systems is species-specific and depends on various ecological and genetic factors, including the burden of MGEs and the fitness effect of HGT in bacterial populations.
Topics: Gene Transfer, Horizontal; Bacteria; Interspersed Repetitive Sequences; CRISPR-Cas Systems; Lysogeny; Species Specificity; Evolution, Molecular
PubMed: 38643972
DOI: 10.1111/1462-2920.16630