This article discusses only the Morpholino antisense oligomers, which are nucleic acid analogs. (wikipedia.org)
Antisense phosphorodiamidate morpholino oligomers (PMOs) are promising candidates to fill such a role, but their challenging synthesis limits their widespread application. (nature.com)
Other morpholino antisense oligomers, viltolarsen and casimersen, have also been approved by the FDA for use in the United States. (medscape.com)
A Novel Zebrafish Model for Assessing In Vivo Delivery of Morpholino Oligomers. (oregonstate.edu)
Morpholino oligomers have great therapeutic potential for treatment of a broad range of human diseases, including viral, bacterial, age-related, and genetic diseases, but they suffer from poor systemic delivery into cells. (oregonstate.edu)
Phosphorodiamidate morpholino oligomers (PMO), which have a neutral chemistry, are extensively being used as tools for selective inhibition of gene expression in cell culture models and are currently in human clinical trials. (psu.edu)
We have recently reported that cell-penetrating peptides (CPPs) and novel chimeric peptides containing CPP (referred as B peptide) and muscle-targeting peptide (referred as MSP) motifs significantly improve the systemic exon-skipping activity of morpholino phosphorodiamidate oligomers (PMOs) in dystrophin-deficient mdx mice. (ox.ac.uk)
Phase II clinical trials in UK and Netherlands have reported induction of dystrophin expression in muscles of DMD patients by systemic administrations of both phosphorodiamidate morpholino oligomers (PMO) and 2'O methyl phosphorothioate. (oregonstate.edu)
Phosphorodiamidate morpholino oligomer5
A Morpholino, also known as a Morpholino oligomer and as a phosphorodiamidate Morpholino oligomer (PMO), is a type of oligomer molecule (colloquially, an oligo) used in molecular biology to modify gene expression. (wikipedia.org)
Morpholino oligos are sometimes referred to as PMO (for phosphorodiamidate morpholino oligomer), especially in medical literature. (wikipedia.org)
Antisense oligonucleotide of the phosphorodiamidate morpholino oligomer (PMO) subclass that binds to exon 53 of dystrophin pre-mRNA. (medscape.com)
Casimersen is an antisense oligonucleotide of the phosphorodiamidate morpholino oligomer (PMO) subclass. (medscape.com)
Our pretargeting strategy uses an anti-human islet cell antibody HPi1, conjugated to a phosphorodiamidate morpholino oligomer (MORF) that binds specifically to a (99m)Tc labeled complementary MORF (cMORF). (nih.gov)
Oligonucleotides5
Chemical technologies can enable such genetic manipulations, as exemplified by the use of caged morpholino (cMO) oligonucleotides to inactivate genes in zebrafish and other optically transparent organisms with spatiotemporal control. (ca.gov)
Title : Nitroreductase-Activatable Morpholino Oligonucleotides for in Vivo Gene Silencing Personal Author(s) : Yamazoe, Sayumi;McQuade, Lindsey E.;Chen, James K. (cdc.gov)
Peptide nanoparticle delivery of charge-neutral splice-switching morpholino oligonucleotides. (ox.ac.uk)
We recently reported that systemic delivery of Morpholino antisense oligonucleotides targeting exon 6 and 8 of the canine DMD gene, efficiently recovered functional dystrophin proteins at the sarcolamma of dystrophic dogs, and improved performance of affected dogs without serious side effects (Yokota et al. (neurology-jp.org)
Antisense morpholino oligonucleotides directed at intronic pseudoexons have been shown to increase propionyl-CoA carboxylase activity to normal levels in fibroblast cell lines derived from patients suffering from propionic acidemia. (medscape.com)
Zebrafish4
Developmental biologists inject Morpholino oligos into eggs or embryos of zebrafish, African clawed frog (Xenopus), sea urchin and killifish (F. heteroclitus) producing morphant embryos, or electroporate Morpholinos into chick embryos at later development stages. (wikipedia.org)
Therefore, we have produced a novel transgenic zebrafish model containing a dual reporter cassette for determination of in vivo delivery, bio-distribution, and safety of a morpholino. (oregonstate.edu)
This chapter provides a description of the reagents, equipment, and procedure for successful retro-orbital injection of a peptide-conjugated morpholino into the blood stream of the adult zebrafish to cause targeted exon skipping in the heart of the zebrafish. (oregonstate.edu)
A prp1 Morpholino injected into zebrafish with mutated prp1 caused significant phenotype at a dose of 6 ng/embryo but had little effect at lower doses (see Supplemental Figure S13). (gene-tools.com)
Oligos4
To help avoid confusion with other morpholine-containing molecules, when describing oligos "Morpholino" is often capitalized as a trade name, but this usage is not consistent across scientific literature. (wikipedia.org)
Morpholino oligos were conceived by Summerton (Gene Tools) at AntiVirals Inc. (now Sarepta Therapeutics) and originally developed in collaboration with Weller. (wikipedia.org)
Morpholino oligos are often used to investigate the role of a specific mRNA transcript in an embryo. (wikipedia.org)
Morpholino oligos (Morpholinos) are widely used tools for knocking down gene expression and are currently in a clinical trial for treatment of Duchene muscular dystrophy. (oregonstate.edu)
Oligonucleotide2
We show here that lipid-functionalized cell-penetrating peptides can be efficiently exploited for cellular transfection of the charge-neutral oligonucleotide analog phosphorodiamidate morpholino. (ox.ac.uk)
The lipopeptides form complexes with splice-switching phosphorodiamidate morpholino oligonucleotide and can be delivered into clinically relevant cell lines that are otherwise difficult to transfect while retaining biological activity. (ox.ac.uk)
Knockdown2
For this purpose, we have carried out morpholino-mediated knockdown of αA-, αBa- and αBb-crystallin and characterized the gross morphology of the lens. (nih.gov)
A more consistent and severe lens phenotype was evident in maternal/zygotic αA-crystallin mutants compared to those observed by morpholino knockdown. (nih.gov)
Systemic1
1997). We also tried systemic delivery of antisense Morpholino to skip exon 51 in mdx52 mice. (neurology-jp.org)
Embryos1
Morpholino knock down of lxr resulted in an overall impaired lipid deposition as determined by oil red O staining particularly in the head and around the eyes, and to significantly elevated levels of both total and free cholesterol in the yolk of lxr morphant embryos. (scirp.org)
Mice2
To optimize therapeutic antisense Morpholinos for more frequent mutations of the DMD gene, we designed antisense Morpholinos targeting exon 51 of the mouse DMD gene, and injected them separately or in combination into the muscles of mdx52 mice, in which exon 52 has been deleted by a gene targeting technique (Araki et al. (neurology-jp.org)
It is important to verify the effectiveness and side effects of antisense Morpholino in experimental animal models such as dystrophic dogs or mdx52 mice, before clinical trials in DMD patients. (neurology-jp.org)
Exon2
The levels of morpholino delivered to the cells in various tissues can be determined by changes in reporter gene expressions caused by morpholino-induced exon skipping. (oregonstate.edu)
Context Dependent Effects of Chimeric Peptide Morpholino Conjugates Contribute to Dystrophin Exon-skipping Efficiency. (ox.ac.uk)
Synthesis1
Versatile synthesis and rational design of caged morpholinos. (ca.gov)
Muscular Dystrophy2
A Morpholino-based drug eteplirsen from Sarepta Therapeutics received accelerated approval from the US Food and Drug Administration in September 2016 for the treatment of some mutations causing Duchenne muscular dystrophy, although the approval process was mired in controversy. (wikipedia.org)
Other Morpholino-based drugs golodirsen, viltolarsen, and casimersen (also for Duchenne muscular dystrophy) were approved by the FDA in 2019-2021. (wikipedia.org)
PPMO1
Vivo-Morpholinos and PPMO are modified forms of Morpholinos with chemical groups covalently attached to facilitate entry into cells. (wikipedia.org)
RNAs1
Techniques for targeting Morpholinos to RNAs and delivering Morpholinos into cells have recently been reviewed in a journal article and in book form. (wikipedia.org)
Vivo delivery1
The need to have an inexpensive vertebrate model for assessing in vivo delivery of morpholinos is evident. (oregonstate.edu)
Phenotype2
Doses of prp1 Morpholino below that threshold produced phenotype at roughly the rate of the standard control oligo injections. (gene-tools.com)
While miR-137 overexpression was not associated with an observable specific phenotype, downregulation by antisense morpholino and/or transgenic expression of miR-sponge RNA induced significant impairment of both embryonic and larval touch-sensitivity without compromising overall anatomical development. (nature.com)
SiRNA1
Morpholinos do not trigger the degradation of their target RNA molecules, unlike many antisense structural types (e.g., phosphorothioates, siRNA). (wikipedia.org)
Genetic diseases1
Morpholinos are in development as pharmaceutical therapeutics targeted against pathogenic organisms such as bacteria or viruses and genetic diseases. (wikipedia.org)
MRNA1
Morpholinos can also modify the splicing of pre-mRNA or inhibit the maturation and activity of miRNA. (wikipedia.org)
Sequence1
Instead, Morpholinos act by "steric blocking", binding to a target sequence within an RNA, inhibiting molecules that might otherwise interact with the RNA. (wikipedia.org)
ACID3
Morpholinos block access of other molecules to small (~25 base) specific sequences of the base-pairing surfaces of ribonucleic acid (RNA). (wikipedia.org)
Morpholinos are synthetic molecules that are the product of a redesign of natural nucleic acid structure. (wikipedia.org)
In terms of structure, the difference between Morpholinos and DNA is that, while Morpholinos have standard nucleic acid bases, those bases are bound to methylenemorpholine rings linked through phosphorodiamidate groups instead of phosphates. (wikipedia.org)
Knocking down gene1
Morpholinos are used as research tools for reverse genetics by knocking down gene function. (wikipedia.org)
Delivery3
With appropriate cytosolic delivery systems, Morpholinos are effective in cell culture. (wikipedia.org)
Vivo-Morpholinos, in which the oligo is covalently linked to a delivery dendrimer, enter cells when administered systemically in adult animals or in tissue cultures. (wikipedia.org)
Although various approaches have been undertaken to address the delivery problem, it remains as the major barrier of morpholinos to be used as effective therapeutics. (oregonstate.edu)
Target1
This is a case where the Morpholino-in-mutant experiment not only detected an off-target interaction of the Morpholino but defined a dose where the effect suddenly became strong. (gene-tools.com)
Cells1
Replacement of anionic phosphates with the uncharged phosphorodiamidate groups eliminates ionization in the usual physiological pH range, so Morpholinos in organisms or cells are uncharged molecules. (wikipedia.org)