319:
trafficking towards the place of action are still largely unclear. Moreover, small differences in ON structure/modification (vide supra) and difference in cell type leads to huge differences in uptake. It is believed that cell uptake occurs on different pathways after adsorption of ONs on the cell surface. Notably, studies show that most tissue culture cells readily take up ASOs (phosphorothiote linkage) in a non-productive way, meaning that no antisense effect is observed. In contrast to that conjugation of ASO with ligands recognised by G-coupled receptors leads to an increased productive uptake. Next to that classification (non-productive vs. productive), cell internalisation mostly proceeds in an energy-dependant way (receptor mediated endocytosis) but energy-independent passive diffusion (gymnosis) may not be ruled out. After passing the cell membrane, ON therapeutics are encapsulated in early
340:. These conjugates are an excellent example for obtaining an increased cell uptake paired with targeted delivery as the corresponding receptors are overexpressed on the target cells leading to a targeted therapeutic (compare antibody-drug conjugates which exploit overexpressed receptors on cancer cells). Another broadly used and heavily investigated entity for targeted delivery and increased cell uptake of oligonucleotides are
2215:
173:
chain. A less than 100% yield of each synthetic step and the occurrence of side reactions set practical limits of the efficiency of the process. In general, oligonucleotide sequences are usually short (13β25 nucleotides long). The maximum length of synthetic oligonucleotides hardly exceeds 200 nucleotide residues.
327:
containing degrading enzymes at low pH. To exert its therapeutic function, the ON needs to escape the endosome prior to its degradation. Currently there is no universal method to overcome the problems of delivery, cell uptake and endosomal escape, but there exist several approaches which are tailored
202:
identification of each nucleotide and the ability to easily follow reactions involving the phosphorothioate nucleotides, which is useful in oligonucleotide synthesis. PS backbone modifications to oligonucleotides protects them against unwanted degradation by enzymes. Modifying the nucleotide backbone
185:
Creating chemically stable short oligonucleotides was the earliest challenge in developing ASO therapies. Naturally occurring oligonucleotides are easily degraded by nucleases, an enzyme that cleaves nucleotides and is ample in every cell type. Short oligonucleotide sequences also have weak intrinsic
331:
A conjugation of ON therapeutics to an entity responsible for cell recognition/uptake not only increases the uptake (vide supra) but is also believed to decrease the complexity of the cell uptake as mainly one (ideally known) mechanism is then involved. This has been achieved with small molecule-ON
318:
Cell uptake/internalisation still represents the biggest hurdle towards successful oligonucleotide (ON) therapeutics. A straightforward uptake, like for most small-molecule drugs, is hindered by the polyanionic backbone and the molecular size of ONs. The exact mechanisms of uptake and intracellular
172:
or, to a lesser extent, of non-nucleosidic compounds. The oligonucleotide chain assembly proceeds in the 3' to 5' direction by following a routine procedure referred to as a "synthetic cycle". Completion of a single synthetic cycle results in the addition of one nucleotide residue to the growing
203:
is widely used because it can be achieved with relative ease and accuracy on most nucleotides. Fluorescent modifications on 5' and 3' end of oligonucleotides was reported to evaluate the oligonucleotides structures, dynamics and interactions with respect to environment.
293:
Neurodegenerative diseases that are a result of a single mutant protein are good targets for antisense oligonucleotide therapies because of their ability to target and modify very specific sequences of RNA with high selectivity. Many genetic diseases including
219:. They also decrease non specific protein binding, increasing the accuracy of targeting specific proteins. Two of the most commonly used modifications are 2'-O-methyl and the 2'-O-methoxyethyl. Fluorescent modifications on the nucleobase was also reported.
1355:
Prakash, Thazha P.; Graham, Mark J.; Yu, Jinghua; Carty, Rick; Low, Audrey; Chappell, Alfred; Schmidt, Karsten; Zhao, Chenguang; Aghajan, Mariam; Murray, Heather F.; Riney, Stan; Booten, Sheri L.; Murray, Susan F.; Gaus, Hans; Crosby, Jeff (July 2014).
364:
stationary phases. Those phases have been investigated for the separation of oligonucleotides. Ion-pair reverse-phase high-performance liquid chromatography is used to separate and analyse the oligonucleotides after automated synthesis.
146:(oligodeoxyribonucleotides), which can be modified at the backbone or on the 2' sugar position to achieve different pharmacological effects. These modifications give new properties to the oligonucleotides and make them a key element in
1091:
Kumar B, Khanna M, Kumar P, Sood V, Vyas R, Banerjea AC (May 2012). "Nucleic acid-mediated cleavage of M1 gene of influenza A virus is significantly augmented by antisense molecules targeted to hybridize close to the cleavage site".
107:, "part"). For example, an oligonucleotide of six nucleotides (nt) is a hexamer, while one of 25 nt would usually be called a "25-mer". Oligonucleotides readily bind, in a sequence-specific manner, to their respective
459:
Yang J, Stolee JA, Jiang H, Xiao L, Kiesman WF, Antia FD, et al. (October 2018). "Solid-Phase
Synthesis of Phosphorothioate Oligonucleotides Using Sulfurization Byproducts for in Situ Capping".
1048:
Kumar P, Kumar B, Rajput R, Saxena L, Banerjea AC, Khanna M (November 2013). "Cross-protective effect of antisense oligonucleotide developed against the common 3' NCR of influenza A virus genome".
1542:
Distler AM, Allison J (April 2001). "5-Methoxysalicylic acid and spermine: a new matrix for the matrix-assisted laser desorption/ionization mass spectrometry analysis of oligonucleotides".
1685:
Gong P, Harbers GM, Grainger DW (April 2006). "Multi-technique comparison of immobilized and hybridized oligonucleotide surface density on commercial amine-reactive microarray slides".
1593:
Shah S, Friedman SH (March 2008). "An ESI-MS method for characterization of native and modified oligonucleotides used for RNA interference and other biological applications".
401:
sequences. One subtype of DNA microarrays can be described as substrates (nylon, glass, etc.) to which oligonucleotides have been bound at high density. There are a number of
397:, oligonucleotide based microarrays have more controlled specificity over hybridization, and the ability to measure the presence and prevalence of alternatively spliced or
1528:
215:. Modifying the 2' position sugar increases the effectiveness of oligonucleotides by enhancing the target binding capabilities of oligonucleotides, specifically in
2231:
310:(ALS) have been linked to DNA alterations that result in incorrect RNA sequences and result in mistranslated proteins that have a toxic physiological effect.
604:
Weiss, B., ed. (1997). Antisense
Oligodeoxynucleotides and Antisense RNA : Novel Pharmacological and Therapeutic Agents. Boca Raton, Florida: CRC Press
257:. RNase H is an enzyme that hydrolyzes RNA, and when used in an antisense oligonucleotide application results in 80-95% down-regulation of mRNA expression.
382:
556:"ASPsiRNA: A Resource of ASP-siRNAs Having Therapeutic Potential for Human Genetic Disorders and Algorithm for Prediction of Their Inhibitory Efficacy"
1810:
61:, these small fragments of nucleic acids can be manufactured as single-stranded molecules with any user-specified sequence, and so are vital for
707:
Frazier KS (January 2015). "Antisense oligonucleotide therapies: the promise and the challenges from a toxicologic pathologist's perspective".
198:(PS) analogs of nucleotides give oligonucleotides some beneficial properties. Key beneficial properties that PS backbones give nucleotides are
174:
1725:
Spingler B (January 2012). "Chapter 3. Metal-Ion-Promoted
Conformational Changes of Oligonucleotides". In Sigel A, Sigel H, Sigel RK (eds.).
385:
mass spectrometry. ElectroSpray
Ionization Mass Spectrometry (ESI-MS) is also a powerful tool to characterize the mass of oligonucleotides.
1358:"Targeted delivery of antisense oligonucleotides to hepatocytes using triantennary N-acetyl galactosamine improves potency 10-fold in mice"
438:
108:
341:
78:
1413:
Buszewski B, Kasturi P, Gilpin RK, Gangoda ME, Jaroniec M (August 1994). "Chromatographic and related studies of alkylamide phases".
1896:
1481:
Gilar, M.; Fountain, K. J.; Budman, Y.; Neue, U. D.; Yardley, K. R.; Rainville, P. D.; Russell Rj, 2nd; Gebler, J. C. (2002-06-07).
216:
132:
2183:
81:. In nature, oligonucleotides are usually found as small RNA molecules that function in the regulation of gene expression (e.g.
2188:
128:
233:
Antisense oligonucleotides (ASO) are single strands of DNA or RNA that are complementary to a chosen sequence. In the case of
429:, the appearance in a population of the same gene in multiple forms because of mutations; can often be tested with ASO probes
2085:
1971:
307:
115:
or, less often, hybrids of a higher order. This basic property serves as a foundation for the use of oligonucleotides as
809:
Eckstein F (April 2000). "Phosphorothioate oligodeoxynucleotides: what is their origin and what is unique about them?".
560:
423:, oligos with non-natural backbones, which do not activate RNase-H but can reduce gene expression or modify RNA splicing
2198:
2193:
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1803:
112:
1483:"Ion-pair reversed-phase high-performance liquid chromatography analysis of oligonucleotides:: Retention prediction"
246:
159:
136:
66:
62:
58:
432:
1186:
Ming, Xin; Alam, Md
Rowshon; Fisher, Michael; Yan, Yongjun; Chen, Xiaoyuan; Juliano, Rudolph L. (2010-06-15).
898:"Probing of Nucleic Acid Structures, Dynamics, and Interactions With Environment-Sensitive Fluorescent Labels"
374:
295:
290:. The antisense oligonucleotides have also been used to inhibit influenza virus replication in cell lines.
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303:
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212:
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for detecting specific sequences of DNA or RNA. Examples of procedures that use oligonucleotides include
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1939:
1522:
1188:"Intracellular delivery of an antisense oligonucleotide via endocytosis of a G protein-coupled receptor"
333:
269:
238:
89:
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2113:
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residues that make up the entire molecule. The length of the oligonucleotide is usually denoted by "
2125:
2108:
1966:
1849:
1009:"Beta-catenin signaling activity dissected in the early Xenopus embryo: a novel antisense approach"
195:
116:
2019:
2014:
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1073:
732:
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85:), or are degradation intermediates derived from the breakdown of larger nucleic acid molecules.
504:"VIRmiRNA: a comprehensive resource for experimentally validated viral miRNAs and their targets"
357:
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2009:
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DNA microarrays are a useful analytical application of oligonucleotides. Compared to standard
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165:
50:
46:
1135:
Smith RA, Miller TM, Yamanaka K, Monia BP, Condon TP, Hung G, et al. (August 2006).
1555:
1450:"Analysis of oligonucleotides by liquid chromatography with alkylamide stationary phase"
913:
640:
615:
249:. Antisense oligonucleotides can be used to target a specific, complementary (coding or
2145:
2048:
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1390:
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1136:
984:
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441:, PPRHs, oligonucleotides that can bind either DNA or RNA and decrease gene expression.
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Another modification that is useful for medical applications of oligonucleotides is
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1983:
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616:"Antisense RNA gene therapy for studying and modulating biological processes"
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which are transported towards late endosomes which are ultimately fused with
177:
and other methods can be used to isolate products with the desired sequence.
164:
Oligonucleotides are chemically synthesized using building blocks, protected
1999:
1783:
1653:
1309:
1248:"Cellular Targeting of Oligonucleotides by Conjugation with Small Molecules"
861:
759:"Antisense oligonucleotides: treating neurodegeneration at the level of RNA"
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1729:. Vol. 10. Springer Science & Business Media. pp. 103β118.
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82:
42:
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253:) RNA. If binding takes place this hybrid can be degraded by the enzyme
2158:
1426:
414:
278:
254:
97:
1698:
1636:
RelΓ³gio A, Schwager C, Richter A, Ansorge W, ValcΓ‘rcel J (June 2002).
846:"Physicochemical properties of phosphorothioate oligodeoxynucleotides"
2173:
2168:
2118:
1325:
1153:
186:
binding affinities, which contributes to their degradation in vivo.
1976:
502:
Qureshi A, Thakur N, Monga I, Thakur A, Kumar M (1 January 2014).
1137:"Antisense oligonucleotide therapy for neurodegenerative disease"
1780:: a database of RNAi libraries and their target analysis results
1792:
1310:"Cellular uptake and trafficking of antisense oligonucleotides"
896:
Michel BY, Dziuba D, Benhida R, Demchenko AP, Burger A (2020).
2038:
1956:
1921:
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1859:
1784:
physorg.com | Genetic source of muscular dystrophy neutralized
276:
and gene function, was first developed by Janet
Heasman using
38:
34:
844:
Stein CA, Subasinghe C, Shinozuka K, Cohen JS (April 1988).
678:"Antisense oligonucleotides: basic concepts and mechanisms"
417:, oligonucleotides with important biological applications
381:
can be used as a matrix for oligonucleotides analysis in
554:
Monga I, Qureshi A, Thakur N, Gupta AK, Kumar M (2017).
1638:"Optimization of oligonucleotide-based DNA microarrays"
1544:
Journal of the
American Society for Mass Spectrometry
2232:
A Review on
Commercial Oligonucleotide Drug Products
1448:
Buszewski B, Safaei Z, StudziΕska S (January 2015).
960:"Molecular Mechanisms of Antisense Oligonucleotides"
2144:
2094:
2037:
1992:
1920:
1875:
1858:
1827:
264:antisense oligonucleotides for gene knockdowns in
245:strands by binding to them, in a process called
1246:Hawner, Manuel; Ducho, Christian (2020-12-16).
1727:Interplay between metal ions and nucleic acids
549:
547:
1804:
811:Antisense & Nucleic Acid Drug Development
8:
45:, that have a wide range of applications in
1527:: CS1 maint: numeric names: authors list (
1872:
1811:
1797:
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1007:Heasman J, Kofron M, Wylie C (June 2000).
435:, an ODN with immunostimulatory properties
88:Oligonucleotides are characterized by the
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139:, and the synthesis of artificial genes.
282:. FDA-approved Morpholino drugs include
451:
328:to specific cells and their receptors.
268:, which is now a standard technique in
1758:
1748:
1520:
614:Weiss B, Davidkova G, Zhou LW (1999).
111:oligonucleotides, DNA, or RNA to form
1303:
1301:
1241:
1239:
1141:The Journal of Clinical Investigation
953:
951:
891:
889:
439:Polypurine reverse-Hoogsteen hairpins
57:. Commonly made in the laboratory by
7:
804:
802:
752:
750:
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746:
671:
669:
667:
620:Cellular and Molecular Life Sciences
217:antisense oligonucleotides therapies
332:conjugates for example bearing an
168:of natural or chemically modified
25:
1935:Micro
757:DeVos SL, Miller TM (July 2013).
142:Oligonucleotides are composed of
133:fluorescent in situ hybridization
2214:
2213:
461:The Journal of Organic Chemistry
1890:precursor, heterogenous nuclear
676:Dias N, Stein CA (March 2002).
403:applications of DNA microarrays
2020:Trans-acting small interfering
1984:Enhancer RNAs
1902:Transfer
59:solid-phase chemical synthesis
1:
1907:Ribosomal
1885:Messenger
1564:10.1016/S1044-0305(01)00212-4
1499:10.1016/S0021-9673(02)00306-0
682:Molecular Cancer Therapeutics
308:amyotrophic lateral sclerosis
272:and is used to study altered
561:G3: Genes, Genomes, Genetics
1735:10.1007/978-94-007-2172-2_3
1487:Journal of Chromatography A
336:which targets receptors of
2263:
2086:Multicopy single-stranded
1930:Interferential
405:within the life sciences.
226:
223:Antisense oligonucleotides
157:
27:Class of short biopolymers
2209:
2000:Guide
1265:10.3390/molecules25245963
1106:10.1007/s12033-011-9437-z
1062:10.1007/s12033-013-9670-8
964:Nucleic Acid Therapeutics
823:10.1089/oli.1.2000.10.117
775:10.1007/s13311-013-0194-5
160:oligonucleotide synthesis
67:polymerase chain reaction
63:artificial gene synthesis
1962:Small nuclear
958:Crooke ST (April 2017).
923:10.3389/fchem.2020.00112
721:10.1177/0192623314551840
433:CpG Oligodeoxynucleotide
207:Sugar ring modifications
2076:Genomic
1094:Molecular Biotechnology
1050:Molecular Biotechnology
520:10.1093/database/bau103
473:10.1021/acs.joc.8b01553
375:5-methoxysalicylic acid
144:2'-deoxyribonucleotides
2179:Artificial chromosomes
1967:Small nucleolar
1642:Nucleic Acids Research
1607:10.1038/nprot.2007.535
1467:10.1515/chem-2015-0141
1362:Nucleic Acids Research
1308:Crooke, S. T. (2017).
1192:Nucleic Acids Research
1026:10.1006/dbio.2000.9720
902:Frontiers in Chemistry
850:Nucleic Acids Research
334:N-acetyl galactosamine
213:2' sugar modifications
190:Backbone modifications
181:Chemical modifications
1972:Small Cajal Body RNAs
1654:10.1093/nar/30.11.e51
1013:Developmental Biology
976:10.1089/nat.2016.0656
862:10.1093/nar/16.8.3209
709:Toxicologic Pathology
632:10.1007/s000180050296
574:10.1534/g3.117.044024
348:Analytical techniques
270:developmental biology
2025:Subgenomic messenger
1940:Small interfering
1912:Transfer-messenger
1687:Analytical Chemistry
314:Cell internalisation
296:Huntington's disease
1556:2001JASMS..12..456D
914:2020FrCh....8..112M
467:(19): 11577β11585.
304:Parkinson's disease
300:Alzheimer's disease
239:protein translation
196:organothiophosphate
2054:Chloroplast
1897:modified Messenger
1860:Ribonucleic acids
1427:10.1007/BF02274494
1374:10.1093/nar/gku531
1204:10.1093/nar/gkq534
2227:
2226:
2104:Xeno
2066:Complementary
2039:Deoxyribonucleic
2033:
2032:
2010:Small hairpin
1699:10.1021/ac051812m
1368:(13): 8796β8807.
1198:(19): 6567β6576.
763:Neurotherapeutics
369:Mass spectrometry
229:Antisense therapy
148:antisense therapy
75:molecular cloning
16:(Redirected from
2254:
2217:
2216:
2194:Yeast
2015:Small temporal
1945:Piwi-interacting
1873:
1869:
1850:Deoxynucleotides
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1806:
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1595:Nature Protocols
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1518:
1493:(1β2): 167β182.
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1326:10.1038/nbt.3779
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568:(9): 2931β2943.
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456:
395:cDNA microarrays
166:phosphoramidites
79:molecular probes
31:Oligonucleotides
21:
18:Oligonucleotides
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2146:Cloning vectors
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2126:Locked
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1421:(3β4): 155β61.
1415:Chromatographia
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1349:
1314:Nat. Biotechnol
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362:chromatographic
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121:DNA microarrays
47:genetic testing
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2109:Glycol
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1914:
1909:
1904:
1899:
1894:
1893:
1892:
1881:
1879:
1870:
1856:
1855:
1853:
1852:
1847:
1842:
1837:
1831:
1829:
1825:
1824:
1821:nucleic acids
1818:
1816:
1815:
1808:
1801:
1793:
1787:
1786:
1781:
1773:
1772:External links
1770:
1768:
1767:
1759:|journal=
1721:
1719:
1716:
1713:
1712:
1693:(7): 2342β51.
1677:
1648:(11): 51eβ51.
1628:
1585:
1534:
1473:
1454:Open Chemistry
1440:
1405:
1347:
1320:(3): 230β237.
1297:
1235:
1178:
1127:
1083:
1040:
999:
947:
885:
856:(8): 3209β21.
836:
798:
742:
699:
663:
606:
597:
543:
494:
450:
449:
447:
444:
443:
442:
436:
430:
424:
418:
410:
407:
399:polyadenylated
390:
389:DNA microarray
387:
370:
367:
354:
353:Chromatography
351:
349:
346:
315:
312:
227:Main article:
224:
221:
208:
205:
191:
188:
182:
179:
158:Main article:
155:
152:
125:Southern blots
71:DNA sequencing
26:
24:
14:
13:
10:
9:
6:
4:
3:
2:
2259:
2248:
2247:Nucleic acids
2245:
2244:
2242:
2233:
2230:
2229:
2220:
2212:
2211:
2208:
2200:
2197:
2195:
2192:
2190:
2187:
2185:
2182:
2181:
2180:
2177:
2175:
2172:
2170:
2167:
2165:
2162:
2160:
2157:
2155:
2152:
2151:
2149:
2147:
2143:
2137:
2134:
2132:
2129:
2127:
2124:
2120:
2117:
2115:
2114:Threose
2112:
2110:
2107:
2106:
2105:
2102:
2101:
2099:
2097:
2093:
2087:
2084:
2082:
2079:
2077:
2074:
2072:
2071:Deoxyribozyme
2069:
2067:
2064:
2060:
2059:Mitochondrial
2057:
2055:
2052:
2051:
2050:
2047:
2046:
2044:
2042:
2036:
2026:
2023:
2021:
2018:
2016:
2013:
2011:
2008:
2006:
2003:
2001:
1998:
1997:
1995:
1991:
1985:
1982:
1978:
1975:
1973:
1970:
1968:
1965:
1963:
1960:
1959:
1958:
1955:
1953:
1950:
1946:
1943:
1941:
1938:
1936:
1933:
1932:
1931:
1928:
1927:
1925:
1923:
1919:
1913:
1910:
1908:
1905:
1903:
1900:
1898:
1895:
1891:
1888:
1887:
1886:
1883:
1882:
1880:
1878:
1877:Translational
1874:
1871:
1867:
1861:
1857:
1851:
1848:
1846:
1843:
1841:
1838:
1836:
1833:
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1830:
1826:
1822:
1814:
1809:
1807:
1802:
1800:
1795:
1794:
1791:
1785:
1782:
1779:
1776:
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1764:
1752:
1744:
1740:
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1732:
1728:
1723:
1722:
1717:
1708:
1704:
1700:
1696:
1692:
1688:
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1678:
1673:
1669:
1664:
1659:
1655:
1651:
1647:
1643:
1639:
1632:
1629:
1624:
1620:
1616:
1612:
1608:
1604:
1600:
1596:
1589:
1586:
1581:
1577:
1573:
1569:
1565:
1561:
1557:
1553:
1550:(4): 456β62.
1549:
1545:
1538:
1535:
1530:
1524:
1516:
1512:
1508:
1504:
1500:
1496:
1492:
1488:
1484:
1477:
1474:
1468:
1463:
1459:
1455:
1451:
1444:
1441:
1436:
1432:
1428:
1424:
1420:
1416:
1409:
1406:
1401:
1397:
1392:
1387:
1383:
1379:
1375:
1371:
1367:
1363:
1359:
1351:
1348:
1343:
1339:
1335:
1331:
1327:
1323:
1319:
1315:
1311:
1304:
1302:
1298:
1293:
1289:
1284:
1279:
1275:
1271:
1266:
1261:
1257:
1253:
1249:
1242:
1240:
1236:
1231:
1227:
1222:
1217:
1213:
1209:
1205:
1201:
1197:
1193:
1189:
1182:
1179:
1174:
1170:
1165:
1160:
1155:
1150:
1147:(8): 2290β6.
1146:
1142:
1138:
1131:
1128:
1123:
1119:
1115:
1111:
1107:
1103:
1099:
1095:
1087:
1084:
1079:
1075:
1071:
1067:
1063:
1059:
1056:(3): 203β11.
1055:
1051:
1044:
1041:
1036:
1032:
1027:
1022:
1019:(1): 124β34.
1018:
1014:
1010:
1003:
1000:
995:
991:
986:
981:
977:
973:
969:
965:
961:
954:
952:
948:
943:
939:
934:
929:
924:
919:
915:
911:
907:
903:
899:
892:
890:
886:
881:
877:
872:
867:
863:
859:
855:
851:
847:
840:
837:
832:
828:
824:
820:
817:(2): 117β21.
816:
812:
805:
803:
799:
794:
790:
785:
780:
776:
772:
769:(3): 486β97.
768:
764:
760:
753:
751:
749:
747:
743:
738:
734:
730:
726:
722:
718:
714:
710:
703:
700:
695:
691:
688:(5): 347β55.
687:
683:
679:
672:
670:
668:
664:
659:
655:
651:
647:
642:
637:
633:
629:
626:(3): 334β58.
625:
621:
617:
610:
607:
601:
598:
593:
589:
584:
579:
575:
571:
567:
563:
562:
557:
550:
548:
544:
539:
535:
530:
525:
521:
517:
513:
509:
505:
498:
495:
490:
486:
482:
478:
474:
470:
466:
462:
455:
452:
445:
440:
437:
434:
431:
428:
425:
422:
419:
416:
413:
412:
408:
406:
404:
400:
396:
388:
386:
384:
380:
376:
373:A mixture of
368:
366:
363:
359:
352:
347:
345:
343:
339:
335:
329:
326:
322:
313:
311:
309:
305:
301:
297:
291:
289:
285:
281:
280:
275:
271:
267:
263:
258:
256:
252:
248:
247:hybridization
244:
243:messenger RNA
240:
237:they prevent
236:
235:antisense RNA
230:
222:
220:
218:
214:
206:
204:
201:
197:
189:
187:
180:
178:
176:
171:
167:
161:
153:
151:
149:
145:
140:
138:
134:
130:
126:
122:
118:
114:
110:
109:complementary
106:
103:
99:
95:
91:
86:
84:
80:
76:
72:
68:
64:
60:
56:
52:
48:
44:
40:
36:
32:
19:
2189:Bacterial
2164:Lambda phage
1828:Constituents
1726:
1690:
1686:
1680:
1645:
1641:
1631:
1601:(3): 351β6.
1598:
1594:
1588:
1547:
1543:
1537:
1523:cite journal
1490:
1486:
1476:
1457:
1453:
1443:
1418:
1414:
1408:
1365:
1361:
1350:
1317:
1313:
1258:(24): 5963.
1255:
1251:
1195:
1191:
1181:
1144:
1140:
1130:
1100:(1): 27β36.
1097:
1093:
1086:
1053:
1049:
1043:
1016:
1012:
1002:
970:(2): 70β77.
967:
963:
905:
901:
853:
849:
839:
814:
810:
766:
762:
715:(1): 78β89.
712:
708:
702:
685:
681:
623:
619:
609:
600:
565:
559:
511:
507:
497:
464:
460:
454:
427:Polymorphism
392:
372:
356:
330:
317:
292:
277:
259:
232:
210:
200:diastereomer
193:
184:
163:
141:
129:ASO analysis
104:
87:
30:
29:
2184:P1-derived
1952:Antisense
1845:Nucleotides
1840:Nucleosides
1835:Nucleobases
421:Morpholinos
358:Alkylamides
338:hepatocytes
266:vertebrates
260:The use of
241:of certain
194:Nucleoside
170:nucleosides
41:molecules,
2136:Morpholino
2049:Organellar
1957:Processual
1922:Regulatory
1866:non-coding
1778:RNAi Atlas
514:: bau103.
446:References
342:antibodies
288:golodirsen
284:eteplirsen
262:Morpholino
251:non-coding
94:nucleotide
33:are short
2096:Analogues
2081:Hachimoji
1864:(coding,
1819:Types of
1761:ignored (
1751:cite book
1507:0021-9673
1382:1362-4962
1274:1420-3049
1252:Molecules
1212:1362-4962
325:lysosomes
321:endosomes
154:Synthesis
55:forensics
43:oligomers
2241:Category
2219:Category
2154:Phagemid
2005:Ribozyme
1743:22210336
1707:16579618
1672:12034852
1615:18323805
1580:18280663
1572:11322192
1515:12134814
1435:97825477
1400:24992960
1334:28244996
1292:33339365
1230:20551131
1173:16878173
1122:45686564
1114:21744034
1078:24496875
1070:23729285
1035:10885751
994:28080221
942:32181238
831:10805163
793:23686823
737:37981276
729:25385330
694:12489851
650:10228554
641:11146801
592:28696921
538:25380780
508:Database
489:52157806
481:30179468
415:Aptamers
409:See also
379:spermine
135:(FISH),
113:duplexes
100:" (from
90:sequence
83:microRNA
51:research
2159:Plasmid
1623:2093309
1552:Bibcode
1391:4117763
1342:1049452
1283:7766908
1221:2965246
1164:1518790
985:5372764
933:7059644
910:Bibcode
908:: 112.
880:2836790
784:3701770
658:9448271
583:5592921
529:4224276
279:Xenopus
255:RNase H
77:and as
69:(PCR),
2174:Fosmid
2169:Cosmid
2119:Hexose
2041:acids
1993:Others
1741:
1705:
1670:
1663:117213
1660:
1621:
1613:
1578:
1570:
1513:
1505:
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1398:
1388:
1380:
1340:
1332:
1290:
1280:
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580:
536:
526:
487:
479:
306:, and
117:probes
53:, and
2199:Human
1977:Y RNA
1619:S2CID
1576:S2CID
1460:(1).
1431:S2CID
1338:S2CID
1118:S2CID
1074:S2CID
733:S2CID
654:S2CID
485:S2CID
383:MALDI
105:meros
102:Greek
1763:help
1739:PMID
1703:PMID
1668:PMID
1611:PMID
1568:PMID
1529:link
1511:PMID
1503:ISSN
1396:PMID
1378:ISSN
1330:PMID
1288:PMID
1270:ISSN
1226:PMID
1208:ISSN
1169:PMID
1110:PMID
1066:PMID
1031:PMID
990:PMID
938:PMID
876:PMID
827:PMID
789:PMID
725:PMID
690:PMID
646:PMID
588:PMID
534:PMID
512:2014
477:PMID
377:and
286:and
175:HPLC
98:-mer
1731:doi
1695:doi
1658:PMC
1650:doi
1603:doi
1560:doi
1495:doi
1491:958
1462:doi
1423:doi
1386:PMC
1370:doi
1322:doi
1278:PMC
1260:doi
1216:PMC
1200:doi
1159:PMC
1149:doi
1145:116
1102:doi
1058:doi
1021:doi
1017:222
980:PMC
972:doi
928:PMC
918:doi
866:PMC
858:doi
819:doi
779:PMC
771:doi
717:doi
636:PMC
628:doi
578:PMC
570:doi
524:PMC
516:doi
469:doi
137:PCR
92:of
39:RNA
37:or
35:DNA
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