CoChat
Sign Up
Cited by 24RNA Interference and Gene DeliveryRNA Research and SplicingRNA regulation and disease

Antisense-Mediated RNA Targeting: Versatile and Expedient Genetic Manipulation in the Brain

Open access
Zalachoras, Ioannis, Evers, Melvin M., van Roon-Mom, Willeke M. C., Aartsma-Rus, Annemieke M., Meijer, Onno C.·2011·Frontiers in Molecular Neuroscience
DOI 10.3389/fnmol.2011.00010PMC PMC3142880
Open this paper in CoChat — free accountOpen PDF

Abstract

A limiting factor in brain research still is the difficulty to evaluate in vivo the role of the increasing number of proteins implicated in neuronal processes. We discuss here the potential of antisense-mediated RNA targeting approaches. We mainly focus on those that manipulate splicing (exon skipping and exon inclusion), but will also briefly discuss mRNA targeting. Classic knockdown of expression by mRNA targeting is only one possible application of antisense oligonucleotides (AON) in the control of gene function. Exon skipping and inclusion are based on the interference of AONs with splicing of pre-mRNAs. These are powerful, specific and particularly versatile techniques, which can be used to circumvent pathogenic mutations, shift splice variant expression, knock down proteins, or to create molecular models using in-frame deletions. Pre-mRNA targeting is currently used both as a research tool, e.g., in models for motor neuron disease, and in clinical trials for Duchenne muscular dystrophy and amyotrophic lateral sclerosis. AONs are particularly promising in relation to brain research, as the modified AONs are taken up extremely fast in neurons and glial cells with a long residence, and without the need for viral vectors or other delivery tools, once inside the blood brain barrier. In this review we cover (1). The principles of antisense-mediated techniques, chemistry, and efficacy. (2) The pros and cons of AON approaches in the brain compared to other techniques of interfering with gene function, such as transgenesis and short hairpin RNAs, in terms of specificity of the manipulation, spatial, and temporal control over gene expression, toxicity, and delivery issues. (3) The potential applications for Neuroscience. We conclude that there is good evidence from animal studies that the central nervous system can be successfully targeted, but the potential of the diverse AON-based approaches appears to be under-recognized.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3389/fnmol.2011.00010

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Two major problems associated with ASOs are the high doses required to achieve gene silencing effects and immunostimulatory effects.

    “However, two major problems associated with ASOs are the high doses required to achieve gene silencing effects and immunostimulatory effects.26,27”

    From Lipid Nanoparticle Delivery of siRNA to Silence Neuronal Gene Expression in the Brain (2013) · cites this paper as [26]

    The Cellular Delivery and Associated Safety section says phosphorothioate antisense oligonucleotides (AONs) can have immunostimulatory effects, while noting that appropriate modifications can suppress them. Neither that section nor the AON Mechanisms section says high doses are required to achieve gene silencing; the paper instead discusses dosage control and possible dose-dependent toxicity. Our copy provides no page numbers for these passages. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 109

  1. Aartsma-Rus A. Janson A. A. Heemskerk J. A. De Winter C. L. Van Ommen G. J. Van Deutekom J. C. (2006). Therapeutic modulation of DMD splicing by blocking exonic splicing enhancer sites with antisense oligonucleotides. Ann. N. Y. Acad. Sci. 1082, 74– 76 10.1196/annals.1348.058 17145928 · DOI
  2. Aartsma-Rus A. van Vliet L. Hirschi M. Janson A. A. Heemskerk H. de Winter C. L. de Kimpe S. van Deutekom J. C. t Hoen P. A. van Ommen G. J. (2009). Guidelines for antisense oligonucleotide design and insight into splice-modulating mechanisms. Mol. Ther. 17, 548– 553 10.1038/mt.2008.205 18813282 PMC2835096 · DOI
  3. Adams M. Meijer O. C. Wang J. Bhargava A. Pearce D. (2003). Homodimerization of the glucocorticoid receptor is not essential for response element binding: activation of the phenylethanolamine N-methyltransferase gene by dimerization-defective mutants. Mol. Endocrinol. 17, 2583– 2592 10.1210/me.2002-0305 12933902 · DOI · Paper page
  4. Agrawal S. Temsamani J. Tang J. Y. (1991). Pharmacokinetics, biodistribution, and stability of oligodeoxynucleotide phosphorothioates in mice. Proc. Natl. Acad. Sci. U.S.A. 88, 7595– 7599 10.1073/pnas.88.17.7595 1881900 PMC52348 · DOI
  5. Al-Chalabi A. Leigh P. N. (2000). Recent advances in amyotrophic lateral sclerosis. Curr. Opin. Neurol. 13, 397– 405 10.1097/00019052-200008000-00006 10970056 · DOI
  6. Alter J. Lou F. Rabinowitz A. Yin H. Rosenfeld J. Wilton S. D. Partridge T. A. Lu Q. L. (2006). Systemic delivery of morpholino oligonucleotide restores dystrophin expression bodywide and improves dystrophic pathology. Nat. Med. 12, 175– 177 10.1038/nm1345 16444267 · DOI
  7. Ambroggi F. Turiault M. Milet A. Deroche-Gamonet V. Parnaudeau S. Balado E. Barik J. van der Veen R. Maroteaux G. Lemberger T. Schutz G. Lazar M. Marinelli M. Piazza P. V. Tronche F. (2009). Stress and addiction: glucocorticoid receptor in dopaminoceptive neurons facilitates cocaine seeking. Nat. Neurosci. 12, 247– 249 10.1038/nn.2282 19234455 · DOI
  8. Baughan T. D. Dickson A. Osman E. Y. Lorson C. L. (2009). Delivery of bifunctional RNAs that target an intronic repressor and increase SMN levels in an animal model of spinal muscular atrophy. Hum. Mol. Genet. 18, 1600– 1611 10.1093/hmg/ddp076 19228773 PMC2667287 · DOI
  9. Bertolino A. Fazio L. Caforio G. Blasi G. Rampino A. Romano R. Di Giorgio A. Taurisano P. Papp A. Pinsonneault J. Wang D. Nardini M. Popolizio T. Sadee W. (2009). Functional variants of the dopamine receptor D2 gene modulate prefronto-striatal phenotypes in schizophrenia. Brain 132, 417– 425 10.1093/brain/awn248 18829695 PMC2640212 · DOI
  10. Blasi G. Lo Bianco L. Taurisano P. Gelao B. Romano R. Fazio L. Papazacharias A. Di Giorgio A. Caforio G. Rampino A. Masellis R. Papp A. Ursini G. Sinibaldi L. Popolizio T. Sadee W. Bertolino A. (2009). Functional variation of the dopamine D2 receptor gene is associated with emotional control as well as brain activity and connectivity during emotion processing in humans. J. Neurosci. 29, 14812– 14819 10.1523/JNEUROSCI.3609-09.2009 19940176 PMC2834475 · DOI
  11. Bogdahn U. Hau P. Stockhammer G. Venkataramana N. K. Mahapatra A. K. Suri A. Balasubramaniam A. Nair S. Oliushine V. Parfenov V. Poverennova I. Zaaroor M. Jachimczak P. Ludwig S. Schmaus S. Heinrichs H. Schlingensiepen K. H. (2011). Targeted therapy for high-grade glioma with the TGF-beta2 inhibitor trabedersen: results of a randomized and controlled phase IIb study. Neurooncology 13, 132– 142 PMC3018908 20980335
  12. Brignole C. Pagnan G. Marimpietri D. Cosimo E. Allen T. M. Ponzoni M. Pastorino F. (2003). Targeted delivery system for antisense oligonucleotides: a novel experimental strategy for neuroblastoma treatment. Cancer Lett. 197, 231– 235 10.1016/S0304-3835(03)00099-5 12880987 · DOI
  13. Burghes A. H. McGovern V. L. (2010). Antisense oligonucleotides and spinal muscular atrophy: skipping along. Genes Dev. 24, 1574– 1579 10.1101/gad.1961710 20679391 PMC2912553 · DOI
  14. Cannella B. Raine C. S. (1995). The adhesion molecule and cytokine profile of multiple sclerosis lesions. Ann. Neurol. 37, 424– 435 10.1002/ana.410370404 7536402 · DOI
  15. Cartegni L. Krainer A. R. (2003). Correction of disease-associated exon skipping by synthetic exon-specific activators. Nat. Struct. Mol. Biol. 10, 120– 125 10.1038/nsb887 12524529 · DOI
  16. Centonze D. Gubellini P. Usiello A. Rossi S. Tscherter A. Bracci E. Erbs E. Tognazzi N. Bernardi G. Pisani A. Calabresi P. Borrelli E. (2004). Differential contribution of dopamine D2S and D2L receptors in the modulation of glutamate and GABA transmission in the striatum. Neuroscience 129, 157– 166 10.1016/j.neuroscience.2004.07.043 15489038 · DOI
  17. Chauhan N. B. Siegel G. J. (2007). Antisense inhibition at the [beta]-secretase-site of [beta]-amyloid precursor protein reduces cerebral amyloid and acetyl cholinesterase activity in Tg2576. Neuroscience 146, 143– 151 10.1016/j.neuroscience.2007.01.008 17303345 PMC1955231 · DOI
  18. Chiasson B. J. Armstrong J. N. Hooper M. L. Murphy P. R. Robertson H. A. (1994). The application of antisense oligonucleotide technology to the brain: some pitfalls. Cell. Mol. Neurobiol. 14, 507– 521 10.1007/BF02088834 7621510 PMC11566955 · DOI
  19. Colelli V. Fiorenza M. T. Conversi D. Orsini C. Cabib S. (2010). Strain-specific proportion of the two isoforms of the dopamine D2 receptor in the mouse striatum: associated neural and behavioral phenotypes. Genes Brain Behav. 9, 703– 711 10.1111/j.1601-183X.2010.00604.x 20546314 · DOI
  20. Cossum P. A. Sasmor H. Dellinger D. Truong L. Cummins L. Owens S. R. Markham P. M. Shea J. P. Crooke S. (1993). Disposition of the 14C-labeled phosphorothioate oligonucleotide ISIS 2105 after intravenous administration to rats. J. Pharmacol. Exp. Ther. 267, 1181– 1190 8166890
  21. Danielian P. S. White R. Lees J. A. Parker M. G. (1992). Identification of a conserved region required for hormone dependent transcriptional activation by steroid hormone receptors. EMBO J. 11, 1025– 1033 1372244 PMC556543
  22. Dash A. K. Cudworth G. C. II. (1998). Therapeutic applications of implantable drug delivery systems. J. Pharmacol. Toxicol. Methods 40, 1– 12 10.1016/S1056-8719(98)00027-6 9920528 · DOI · Paper page
  23. De Mei C. Ramos M. Iitaka C. Borrelli E. (2009). Getting specialized: presynaptic and postsynaptic dopamine D2 receptors. Curr. Opin. Pharmacol. 9, 53– 58 10.1016/j.coph.2008.12.002 19138563 PMC2710814 · DOI
  24. Di Benedetto B. Wefers B. Wurst W. Kuhn R. (2009). Local knockdown of ERK2 in the adult mouse brain via adeno-associated virus-mediated RNA interference. Mol. Biotechnol. 41, 263– 269 10.1007/s12033-008-9140-x 19052925 PMC2758379 · DOI
  25. Dias N. Stein C. A. (2002). Antisense oligonucleotides: basic concepts and mechanisms. Mol. Cancer Ther. 1, 347– 355 12489851
  26. Dickson A. Osman E. Lorson C. L. (2008). A negatively acting bifunctional RNA increases survival motor neuron both in vitro and in vivo. Hum. Gene Ther. 19, 1307– 1315 10.1089/hum.2008.067 19848583 PMC2940461 · DOI
  27. Driesse M. J. Esandi M. C. Kros J. M. Avezaat C. J. Vecht C. Zurcher C. van der Velde I. Valerio D. Bout A. Sillevis Smitt P. A. (2000). Intra-CSF administered recombinant adenovirus causes an immune response-mediated toxicity. Gene Ther. 7, 1401– 1409 10.1038/sj.gt.3301250 10981667 · DOI
  28. Ehlert E. M. Eggers R. Niclou S. P. Verhaagen J. (2010). Cellular toxicity following application of adeno-associated viral vector-mediated RNA interference in the nervous system. BMC Neurosci. 11, 20 10.1186/1471-2202-11-20 20167052 PMC2841193 · DOI
  29. Fazio L. Blasi G. Taurisano P. Papazacharias A. Romano R. Gelao B. Ursini G. Quarto T. Lo Bianco L. Di Giorgio A. Mancini M. Popolizio T. Rubini G. Bertolino A. (2011). D2 receptor genotype and striatal dopamine signaling predict motor cortical activity and behavior in humans. Neuroimage 54, 2915– 2921 10.1016/j.neuroimage.2010.11.034 21087673 · DOI
  30. Fetsko L. A. Xu R. Wang Y. (2005). Effects of age and dopamine D2L receptor-deficiency on motor and learning functions. Neurobiol. Aging 26, 521– 530 10.1016/j.neurobiolaging.2004.04.005 15653180 · DOI
  31. Gaglione M. Messere A. (2010). Recent progress in chemically modified siRNAs. Mini Rev. Med. Chem. 10, 578– 595 10.2174/138955710791384036 20500149 · DOI
  32. Giguere V. Hollenberg S. M. Rosenfeld M. G. Evans R. M. (1986). Functional domains of the human glucocorticoid receptor. Cell 46, 645– 652 10.1016/0092-8674(86)90339-9 3742595 · DOI
  33. Glatt S. J. Faraone S. V. Lasky-Su J. A. Kanazawa T. Hwu H. G. Tsuang M. T. (2009). Family-based association testing strongly implicates DRD2 as a risk gene for schizophrenia in Han Chinese from Taiwan. Mol. Psychiatry 14, 885– 893 10.1038/mp.2008.30 18332877 PMC2755547 · DOI
  34. Goemans N. M. Tulinius M. van den Akker J. T. Burm B. E. Ekhart P. F. Heuvelmans N. Holling T. Janson A. A. Platenburg G. J. Sipkens J. A. Sitsen J. M. Aartsma-Rus A. van Ommen G. J. Buyse G. Darin N. Verschuuren J. J. Campion G. V. de Kimpe S. J. van Deutekom J. C. (2011). Systemic administration of PRO051 in Duchenne’s muscular dystrophy. N. Engl. J. Med. 364, 1513– 1522 10.1056/NEJMoa1011367 21428760 · DOI
  35. Grimm D. Streetz K. L. Jopling C. L. Storm T. A. Pandey K. Davis C. R. Marion P. Salazar F. Kay M. A. (2006). Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Nature 441, 537– 541 10.1038/nature04791 16724069 · DOI · Paper page
  36. Guterstam P. Lindgren M. Johansson H. Tedebark U. Wengel J. El Andaloussi S. Langel Ü. (2008). Splice-switching efficiency and specificity for oligonucleotides with locked nucleic acid monomers. Biochem. J. 412, 307– 313 10.1042/BJ20080013 18271753 · DOI
  37. Hamm S. Latz E. Hangel D. Müller T. Yu P. Golenbock D. Sparwasser T. Wagner H. Bauer S. (2010). Alternating 2′-O-ribose methylation is a universal approach for generating non-stimulatory siRNA by acting as TLR7 antagonist. Immunobiology 215, 559– 569 10.1016/j.imbio.2009.09.003 19854535 · DOI
  38. Heemskerk H. de Winter C. van Kuik P. Heuvelmans N. Sabatelli P. Rimessi P. Braghetta P. van Ommen G. J. de Kimpe S. Ferlini A. Aartsma-Rus A. van Deutekom J. C. (2010). Preclinical PK and PD studies on 2′-O-methyl-phosphorothioate RNA antisense oligonucleotides in the mdx mouse model. Mol. Ther. 18, 1210– 1217 10.1038/mt.2010.72 20407428 PMC2889733 · DOI
  39. Heemskerk H. A. de Winter C. L. de Kimpe S. J. van Kuik-Romeijn P. Heuvelmans N. Platenburg G. J. van Ommen G. J. van Deutekom J. C. Aartsma-Rus A. (2009). In vivo comparison of 2′-O-methyl phosphorothioate and morpholino antisense oligonucleotides for Duchenne muscular dystrophy exon skipping. J. Gene Med 11, 257– 66 10.1002/jgm.1288 19140108 · DOI
  40. Hemmings-Mieszczak M. Dorn G. Natt F. J. Hall J. Wishart W. L. (2003). Independent combinatorial effect of antisense oligonucleotides and RNAi-mediated specific inhibition of the recombinant Rat P2X3 receptor. Nucleic Acids Res. 31, 2117– 2126 10.1093/nar/gkg322 12682362 PMC153750 · DOI
  41. Hua Y. Sahashi K. Hung G. Rigo F. Passini M. A. Bennett C. F. Krainer A. R. (2010). Antisense correction of SMN2 splicing in the CNS rescues necrosis in a type III SMA mouse model. Genes Dev. 24, 1634– 1644 10.1101/gad.1941310 20624852 PMC2912561 · DOI
  42. Iorns E. Lord C. J. Turner N. Ashworth A. (2007). Utilizing RNA interference to enhance cancer drug discovery. Nat. Rev. Drug Discov. 6, 556– 568 10.1038/nrd2355 17599085 · DOI
  43. Jayandharan G. R. Aslanidi G. Martino A. T. Jahn S. C. Perrin G. Q. Herzog R. W. Srivastava A. (2011). Activation of the NF-κB pathway by adeno-associated virus (AAV) vectors and its implications in immune response and gene therapy. Proc. Natl. Acad. Sci. U.S.A. 108, 3743– 3748 10.1073/pnas.1012753108 21321191 PMC3048154 · DOI
  44. Kaplitt M. G. Darakchiev B. During M. J. (1998). Prospects for gene therapy in pediatric neurosurgery. Pediatr. Neurosurg. 28, 3– 14 10.1159/000028611 9693323 · DOI
  45. Kinali M. Arechavala-Gomeza V. Feng L. Cirak S. Hunt D. Adkin C. Guglieri M. Ashton E. Abbs S. Nihoyannopoulos P. Elena Garralda M. Rutherford M. McCulley C. Popplewell L. Graham I. R. Dickson G. Wood M. J. A. Wells D. J. Wilton S. D. Kole R. Straub V. Bushby K. Sewry C. Morgan J. E. Muntoni F. (2009). Local restoration of dystrophin expression with the morpholino oligomer AVI-4658 in Duchenne muscular dystrophy: a single-blind, placebo-controlled, dose-escalation, proof-of-concept study. Lancet Neurol. 8, 918– 928 10.1016/S1474-4422(09)70211-X 19713152 PMC2755039 · DOI
  46. Kolber B. J. Roberts M. S. Howell M. P. Wozniak D. F. Sands M. S. Muglia L. J. (2008). Central amygdala glucocorticoid receptor action promotes fear-associated CRH activation and conditioning. Proc. Natl. Acad. Sci. U.S.A. 105, 12004– 12009 10.1073/pnas.0803216105 18695245 PMC2575312 · DOI
  47. Krebs M. D. Alsberg E. (2011). Localized, targeted, and sustained siRNA delivery. Chem. Eur. J. 17, 3054– 3062 10.1002/chem.201003144 PMC7162106 21341332 · DOI
  48. Kubo K. Tomita K. Uto A. Kuroda K. Seshadri S. Cohen J. Kaibuchi K. Kamiya A. Nakajima K. (2010). Migration defects by DISC1 knockdown in C57BL/6, 129X1/SvJ, and ICR strains via in utero gene transfer and virus-mediated RNAi. Biochem. Biophys. Res. Commun. 400, 631– 637 10.1016/j.bbrc.2010.08.117 20807500 PMC2949544 · DOI
  49. Lachize S. Apostolakis E. M. van der Laan S. Tijssen A. M. Xu J. de Kloet E. R. Meijer O. C. (2009). Steroid receptor coactivator-1 is necessary for regulation of corticotropin-releasing hormone by chronic stress and glucocorticoids. Proc. Natl. Acad. Sci. U.S.A. 106, 8038– 8042 10.1073/pnas.0812062106 19416907 PMC2683087 · DOI
  50. Liang X. H. Crooke S. T. (2011). Depletion of key protein components of the RISC pathway impairs pre-ribosomal RNA processing. Nucleic Acids Res. 39, 4875– 4889 10.1093/nar/gkr351 21321021 PMC3113584 · DOI
  51. Liebsch G. Landgraf R. Engelmann M. Lorscher P. Holsboer F. (1999). Differential behavioural effects of chronic infusion of CRH1 and CRH2 receptor antisense oligonucleotides into the rat brain. J. Psychiatr. Res. 33, 153– 163 10.1016/S0022-3956(98)80047-2 10221747 · DOI
  52. Lim S. R. Hertel K. J. (2001). Modulation of survival motor neuron pre-mRNA splicing by inhibition of alternative 3′ splice site pairing. J. Biol. Chem. 276, 45476– 45483 10.1074/jbc.M101114200 11584013 · DOI
  53. Liu Q. R. Pan C. H. Hishimoto A. Li C. Y. Xi Z. X. Llorente-Berzal A. Viveros M. P. Ishiguro H. Arinami T. Onaivi E. S. Uhl G. R. (2009). Species differences in cannabinoid receptor 2 (CNR2 gene): identification of novel human and rodent CB2 isoforms, differential tissue expression and regulation by cannabinoid receptor ligands. Genes Brain Behav. 8, 519– 530 10.1111/j.1601-183X.2009.00498.x 19496827 PMC3389515 · DOI
  54. Lobb R. R. Hemler M. E. (1994). The pathophysiologic role of alpha 4 integrins in vivo. J. Clin. Invest. 94, 1722– 1728 10.1172/JCI117519 7525645 PMC294562 · DOI
  55. Lu Q. L. Mann C. J. Lou F. Bou-Gharios G. Morris G. E. Xue S. A. Fletcher S. Partridge T. A. Wilton S. D. (2003). Functional amounts of dystrophin produced by skipping the mutated exon in the mdx dystrophic mouse. Nat. Med. 9, 1009– 1014 10.1038/nm806 12847521 · DOI
  56. Ma L. Wang D. D. Zhang T. Y. Yu H. Wang Y. Huang S. H. Lee F. S. Chen Z. Y. (2011). Region-specific involvement of BDNF secretion and synthesis in conditioned taste aversion memory formation. J. Neurosci. 31, 2079– 2090 10.1523/JNEUROSCI.6566-10.2011 21307245 PMC3044502 · DOI
  57. Ma Y. Creanga A. Lum L. Beachy P. A. (2006). Prevalence of off-target effects in Drosophila RNA interference screens. Nature 443, 359– 363 10.1038/nature05179 16964239 · DOI
  58. Markovic D. Lehnert H. Levine M. A. Grammatopoulos D. K. (2008). Structural determinants critical for localization and signaling within the seventh transmembrane domain of the type 1 corticotropin releasing hormone receptor: lessons from the receptor variant R1d. Mol. Endocrinol. 22, 2505– 2519 10.1210/me.2008-0177 18772229 · DOI
  59. Marwick C. (1998). First “antisense” drug will treat CMV retinitis. JAMA 280, 871 10.1001/jama.280.13.1126 9739955 · DOI
  60. Mittelstadt P. R. Ashwell J. D. (2003). Disruption of glucocorticoid receptor exon 2 yields a ligand-responsive C-terminal fragment that regulates gene expression. Mol. Endocrinol. 17, 1534– 1542 10.1210/me.2002-0429 12750452 · DOI
  61. Moyer R. A. Wang D. Papp A. C. Smith R. M. Duque L. Mash D. C. Sadee W. (2011). Intronic polymorphisms affecting alternative splicing of human dopamine D2 receptor are associated with cocaine abuse. Neuropsychopharmacology 36, 753– 762 10.1038/npp.2010.208 21150907 PMC3055737 · DOI
  62. Muller Y. L. Reitstetter R. Yool A. J. (2000). Antisense knockdown of calcium-dependent K+ channels in developing cerebellar Purkinje neurons. Dev. Brain Res. 120, 135– 140 10.1016/S0165-3806(00)00004-3 10775766 · DOI
  63. Myers K. J. Witchell D. R. Graham M. J. Koo S. Butler M. Condon T. P. (2005). Antisense oligonucleotide blockade of alpha 4 integrin prevents and reverses clinical symptoms in murine experimental autoimmune encephalomyelitis. J. Neuroimmunol. 160, 12– 24 10.1016/j.jneuroim.2004.10.029 15710453 · DOI
  64. Naldini L. Blomer U. Gallay P. Ory D. Mulligan R. Gage F. H. Verma I. M. Trono D. (1996). In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 272, 263– 267 10.1126/science.272.5259.263 8602510 · DOI · Paper page
  65. Nasevicius A. Ekker S. C. (2000). Effective targeted gene “knockdown” in zebrafish. Nat. Genet. 26, 216– 220 10.1038/79951 11017081 · DOI
  66. Nasevicius A. Larson J. Ekker S. C. (2000). Distinct requirements for zebrafish angiogenesis revealed by a VEGF-A morphant. Yeast 17, 294– 301 10.1002/1097-0061(200012)17:4<294::AID-YEA54>3.0.CO;2-5 11119306 PMC2448381 · DOI
  67. Nlend Nlend R. Meyer K. Schumperli D. (2010). Repair of pre-mRNA splicing: prospects for a therapy for spinal muscular atrophy. RNA Biol. 7, 430– 440 10.4161/rna.7.4.12206 20523126 PMC3070909 · DOI
  68. Oitzl M. S. Reichardt H. M. Joels M. de Kloet E. R. (2001). Point mutation in the mouse glucocorticoid receptor preventing DNA binding impairs spatial memory. Proc. Natl. Acad. Sci. U.S.A. 98, 12790– 12795 10.1073/pnas.231313998 11606764 PMC60132 · DOI
  69. Okun E. Lathia J. D. Mattson M. P. (2009). Adhesion- and migration-related side effects of phosphothioated CpG oligodeoxynucleotides. Cell Adh. Migr. 3, 272– 274 10.4161/cam.3.3.8692 19458479 PMC2712808 · DOI
  70. Olbricht W. L. Neeves K. B. Foley C. P. (2010). Microfluidic probes in the treatment of brain-related diseases. Drug News Perspect. 23, 491– 497 21031165
  71. Oshiro E. M. Viola J. J. Oldfield E. H. Walbridge S. Bacher J. Frank J. A. Blaese R. M. Ram Z. (1995). Toxicity studies and distribution dynamics of retroviral vectors following intrathecal administration of retroviral vector-producer cells. Cancer Gene Ther. 2, 87– 95 7621261
  72. Pan Q. de Ruiter P. E. von Eije K. J. Smits R. Kwekkeboom J. Tilanus H. W. Berkhout B. Janssen H. L. van der Laan L. J. (2011). Disturbance of the microRNA pathway by commonly used lentiviral shRNA libraries limits the application for screening host factors involved in hepatitis C virus infection. FEBS Lett. 585, 1025– 1030 10.1016/j.febslet.2011.02.035 21376045 · DOI
  73. Pardridge W. M. (2002). Drug and gene targeting to the brain with molecular trojan horses. Nat. Rev. Drug Discov. 1, 131– 139 10.1038/nrd725 12120094 · DOI
  74. Passini M. A. Bu J. Richards A. M. Kinnecom C. Sardi S. P. Stanek L. M. Hua Y. Rigo F. Matson J. Hung G. Kaye E. M. Shihabuddin L. S. Krainer A. R. Bennett C. F. Cheng S. H. (2011). Antisense oligonucleotides delivered to the mouse CNS ameliorate symptoms of severe spinal muscular atrophy. Sci. Transl. Med. 3, 72ra18 21368223 PMC3140425
  75. Petri S. Dueck A. Lehmann G. Putz N. Rüdel S. Kremmer E. Meister G. (2011). Increased siRNA duplex stability correlates with reduced off-target and elevated on-target effects. RNA 17, 737– 749 10.1261/rna.2348111 21367974 PMC3062184 · DOI
  76. Pfeifer A. Brandon E. P. Kootstra N. F. Gage H. Verma I. M. (2001). Delivery of the Cre recombinase by a self-deleting lentiviral vector: efficient gene targeting in vivo. Proc. Natl. Acad. Sci. U.S.A. 98, 11450– 11455 10.1073/pnas.201415498 11553794 PMC58750 · DOI
  77. Pitts M. W. Takahashi L. K. (2010). The central amygdala nucleus via corticotropin-releasing factor is necessary for time-limited consolidation processing but not storage of contextual fear memory. Neurobiol. Learn. Mem. 95, 86– 91 10.1016/j.nlm.2010.11.006 21093597 PMC3022075 · DOI
  78. Pitts M. W. Todorovic C. Blank T. Takahashi L. K. (2009). The central nucleus of the amygdala and corticotropin-releasing factor: insights into contextual fear memory. J. Neurosci. 29, 7379– 7388 10.1523/JNEUROSCI.0740-09.2009 19494159 PMC2771694 · DOI
  79. Riley M. Gary I. Norman Kim N. Vance Watson E. Pierre Gobin Y. LeBel C. P. Black K. L. Bartus R. T. (1998). Intra-arterial administration of carboplatin and the blood brain barrier permeabilizing agent, RMP-7: a toxicologic evaluation in swine. J. Neurooncol. 36, 167– 178 10.1023/A:1005751922174 9525816 · DOI
  80. Robbins M. Judge A. Liang L. McClintock K. Yaworski E. MacLachlan I. (2007). 2′-O-methyl-modified RNAs act as TLR7 antagonists. Mol. Ther. 15, 1663– 1669 10.1038/sj.mt.6300240 17579574 · DOI
  81. Rose D. M. Alon R. Ginsberg M. H. (2007). Integrin modulation and signaling in leukocyte adhesion and migration. Immunol. Rev. 218, 126– 134 10.1111/j.1600-065X.2007.00536.x 17624949 · DOI · Paper page
  82. Ryberg E. Vu H. K. Larsson N. Groblewski T. Hjorth S. Elebring T. Sjögren S. Greasley P. J. (2005). Identification and characterisation of a novel splice variant of the human CB1 receptor. FEBS Lett. 579, 259– 264 10.1016/j.febslet.2004.11.085 15620723 · DOI
  83. Sah D. W. Y. Aronin N. (2011). Oligonucleotide therapeutic approaches for Huntington disease. J. Clin. Invest. 121, 500– 507 10.1172/JCI45130 21285523 PMC3026739 · DOI
  84. Sanchez C. E. Tierney T. S. Gale J. T. Alavian K. N. Sahin A. Lee J. S. Mulligan R. C. Carter B. S. (2011). Recombinant adeno-associated virus type 2 pseudotypes: comparing safety, specificity, and transduction efficiency in the primate striatum. J. Neurosurg. 114, 672– 680 10.3171/2010.8.JNS091583 20950087 PMC3773229 · DOI
  85. Selkoe D. Kopan R. (2003). Notch and presenilin: regulated intramembrane proteolysis links development and degeneration. Annu. Rev. Neurosci. 26, 565– 597 10.1146/annurev.neuro.26.041002.131334 12730322 · DOI
  86. Shim M. S. Kwon Y. J. (2010). Efficient and targeted delivery of siRNA in vivo. FEBS J. 277, 4814– 4827 10.1111/j.1742-4658.2010.07904.x 21078116 · DOI
  87. Singh N. K. Singh N. N. Androphy E. J. Singh R. N. (2006). Splicing of a critical exon of human survival motor neuron is regulated by a unique silencer element located in the last intron. Mol. Cell. Biol. 26, 1333– 1346 10.1128/MCB.26.4.1333-1346.2006 16449646 PMC1367187 · DOI
  88. Sioud M. Furset G. Cekaite L. (2007). Suppression of immunostimulatory siRNA-driven innate immune activation by 2′-modified RNAs. Biochem. Biophys. Res. Commun. 361, 122– 126 10.1016/j.bbrc.2007.06.177 17658482 · DOI
  89. Skordis L. A. Dunckley M. G. Yue B. Eperon I. C. Muntoni F. (2003). Bifunctional antisense oligonucleotides provide a trans-acting splicing enhancer that stimulates SMN2 gene expression in patient fibroblasts. Proc. Natl. Acad. Sci. U.S.A. 100, 4114– 4119 10.1073/pnas.0633863100 12642665 PMC153057 · DOI
  90. Sledz C. A. Holko M. de Veer M. J. Silverman R. H. Williams B. R. G. (2003). Activation of the interferon system by short-interfering RNAs. Nat. Cell Biol. 5, 834– 839 10.1038/ncb1038 12942087 · DOI
  91. Smith R. A. Miller T. M. Yamanaka K. Monia B. P. Condon T. P. Hung G. Lobsiger C. S. Ward C. M. McAlonis-Downes M. Wei H. Wancewicz E. V. Bennett C. F. Cleveland D. W. (2006). Antisense oligonucleotide therapy for neurodegenerative disease. J. Clin. Investig. 116, 2290– 2296 10.1172/JCI25424 16878173 PMC1518790 · DOI · Paper page
  92. Stein C. A. Bo Hansen J. Lai J. Wu S. Voskresenskiy A. Høg A. Worm J. Hedtjärn M. Souleimanian N. Miller P. Soifer H. S. Castanotto D. Benimetskaya L. Ørum H. Koch T. (2010). Efficient gene silencing by delivery of locked nucleic acid antisense oligonucleotides, unassisted by transfection reagents. Nucleic Acids Res. 38, e3 10.1093/nar/gkq553 19854938 PMC2800216 · DOI
  93. Tan S. Hermann B. Borrelli E. (2003). Dopaminergic mouse mutants: Investigating the roles of the different dopamine receptor subtypes and the dopamine transporter. Int. Rev. Neurobiol. 54, 145– 197 10.1016/S0074-7742(03)54005-3 12785287 · DOI
  94. Trifonov S. Houtani T. Shimizu J. Hamada S. Kase M. Maruyama M. Sugimoto T. (2010). GPR155: gene organization, multiple mRNA splice variants and expression in mouse central nervous system. Biochem. Biophys. Res. Commun. 398, 19– 25 10.1016/j.bbrc.2010.05.162 20537985 · DOI
  95. Ulusoy A. Decressac M. Kirik D. Bjorklund A. (2010). Viral vector-mediated overexpression of alpha-synuclein as a progressive model of Parkinson’s disease. Prog. Brain Res. 184, 89– 111 20887871
  96. Vallone D. Picetti R. Borrelli E. (2000). Structure and function of dopamine receptors. Neurosci. Biobehav. Rev. 24, 125– 132 10.1016/S0149-7634(99)00063-9 10654668 · DOI
  97. Van Broeck B. Van Broeckhoven C. Kumar-Singh S. (2007). Current insights into molecular mechanisms of alzheimer disease and their implications for therapeutic approaches. Neurodegener. Dis. 4, 349– 365 10.1159/000105156 17622778 · DOI
  98. van der Laan S. Lachize S. B. Vreugdenhil E. de Kloet E. R. Meijer O. C. (2008). Nuclear receptor coregulators differentially modulate induction and glucocorticoid receptor-mediated repression of the corticotropin-releasing hormone gene. Endocrinology 149, 725– 732 10.1210/en.2007-1234 18006628 · DOI
  99. van Deutekom J. C. Janson A. A. Ginjaar I. B. Frankhuizen W. S. Aartsma-Rus A. Bremmer-Bout M. den Dunnen J. T. Koop K. van der Kooi A. J. Goemans N. M. de Kimpe S. J. Ekhart P. F. Venneker E. H. Platenburg G. J. Verschuuren J. J. van Ommen G. J. B. (2007). Local dystrophin restoration with antisense oligonucleotide PRO051. N. Engl. J. Med. 357, 2677– 2686 10.1056/NEJMoa073108 18160687 · DOI
  100. van Ham II Banihashemi B. Wilson A. M. Jacobsen K. X. Czesak M. Albert P. R. (2007). Differential signaling of dopamine-D2S and -D2L receptors to inhibit ERK1/2 phosphorylation. J. Neurochem. 102, 1796– 1804 10.1111/j.1471-4159.2007.04650.x 17767702 · DOI
  101. Vickers T. A. Lima W. F. Wu H. Nichols J. G. Linsley P. S. Crooke S. T. (2009). Off-target and a portion of target-specific siRNA mediated mRNA degradation is Ago2 “slicer” independent and can be mediated by Ago1. Nucleic Acids Res. 37, 6927– 6941 10.1093/nar/gkp735 19767612 PMC2777430 · DOI
  102. Voigt T. Meyer K. Baum O. Schümperli D. (2010). Ultrastructural changes in diaphragm neuromuscular junctions in a severe mouse model for spinal muscular atrophy and their prevention by bifunctional U7 snRNA correcting SMN2 splicing. Neuromuscul. Disord. 20, 744– 752 10.1016/j.nmd.2010.06.010 20832308 · DOI
  103. Wang Y. Y. Xu R. Sasaoka T. Tonegawa S. Kung M. P. Sankoorikal E. B. (2000). Dopamine D2 long receptor-deficient mice display alterations in striatum-dependent functions. J. Neurosci. 20, 8305– 8314 11069937 PMC6773184
  104. Williams J. H. Schray R. C. Patterson C. A. Ayitey S. O. Tallent M. K. Lutz G. J. (2009). Oligonucleotide-mediated survival of motor neuron protein expression in CNS improves phenotype in a mouse model of spinal muscular atrophy. J. Neurosci. 29, 7633– 7638 10.1523/JNEUROSCI.0980-08.2009 19535574 PMC6665627 · DOI
  105. Woldbye D. P. Angehagen M. Gotzsche C. R. Elbrond-Bek H. A. Sorensen T. Christiansen S. H. Olesen M. V. Nikitidou L. Hansen T. V. Kanter-Schlifke I. Kokaia M. (2010). Adeno-associated viral vector-induced overexpression of neuropeptide Y Y2 receptors in the hippocampus suppresses seizures. Brain 133, 2778– 2788 10.1093/brain/awq219 20688813 · DOI
  106. Xu R. Hranilovic D. Fetsko L. A. Bucan M. Wang Y. (2002). Dopamine D2S and D2L receptors may differentially contribute to the actions of antipsychotic and psychotic agents in mice. Mol. Psychiatry 7, 1075– 1082 10.1038/sj.mp.4001145 12476322 · DOI
  107. Yoo B. H. Bochkareva E. Bochkarev A. Mou T. C. Gray D. M. (2004). 2′-O-methyl-modified phosphorothioate antisense oligonucleotides have reduced non-specific effects in vitro. Nucleic Acids Res. 32, 2008– 2016 10.1093/nar/gkh516 15064360 PMC390367 · DOI
  108. Zhang Y. Jeong Lee H. Boado R. J. Pardridge W. M. (2002). Receptor-mediated delivery of an antisense gene to human brain cancer cells. J. Gene Med. 4, 183– 194 10.1002/jgm.255 11933219 · DOI
  109. Zmijewski M. A. Slominski A. T. (2009). Modulation of corticotropin releasing factor (CRF) signaling through receptor splicing in mouse pituitary cell line AtT-20 – emerging role of soluble isoforms. J. Physiol. Pharmacol. 60(Suppl. 4), 39– 46 20083850 PMC2814449

Cited by

Sorted by citations

Authors
Zalachoras, I., Evers, M. M., van Roon-Mom, W. M. C., Aartsma-Rus, A. M., & Meijer, O. C.
Affiliations
Leiden University Medical Center (NL)
Corresponding author
Meijer, Onno C.
ORCID
Venue
Frontiers in Molecular Neuroscience
Publisher
Frontiers Media SA
Published
2011
Volume
4
Pages
10-10
ISSN
1662-5099 (ISSN-L)
DOI
10.3389/fnmol.2011.00010
PMC
PMC3142880
OpenAlex
W2166647794
Cited by
24
References
4
Citations by year
2025: 1 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 4 · 2016: 1 · 2014: 3 · 2013: 7 · 2012: 5
FWCI
1.95
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Molecular Neuroscience (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Leiden Repository (Leiden University) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
Keywords
antisense oligonucleotides, RNA targeting, exon skipping, exon inclusion, pre-mRNA splicing, mRNA targeting, gene knockdown, brain research, central nervous system targeting, blood-brain barrier, neuronal uptake, Duchenne muscular dystrophy, amyotrophic lateral sclerosis, in-frame deletion, splice variants

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review