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Morpholinos in diagnostic applications

Morpholinos have been used as probes in many styles of diagnostic systems. Their complete resistance to nucleases and their absence of electrostatic charge at neutral pH allow development of novel diagnostic applications. Here are some citations from those projects.

Li H, Wu C, Aramayo R, Sachs MS, Harlow ML. Synaptic vesicles contain small ribonucleic acids (sRNAs) including transfer RNA fragments (trfRNA) and microRNAs (miRNA). Sci Rep. 2015 Oct 8;5:14918. doi: 10.1038/srep14918.
Morpholino used as an in situ probe.

Qiao W, Chiang H-C, Xie H, Levicky R. Surface vs. solution hybridization: effects of salt, temperature, and probe type. Chem Commun. 2015;[Epub ahead of print] doi:10.1039/C5CC06674C

Burki U, Keane J, Blain A, O'Donovan L, Gait MJ, Laval SH, Straub V. Development and Application of an Ultrasensitive Hybridization-Based ELISA Method for the Determination of Peptide-Conjugated Phosphorodiamidate Morpholino Oligonucleotides. Nucleic Acid Ther. 2015 Jul 15. [Epub ahead of print]

Hu W, Ning Y, Li L, Kong J, Zhang X. Highly sensitive detection of sequence-specific DNA with morpholino-functionalized magnetic microspheres. Anal Methods. 2015;[Epub ahead of print] doi:10.1039/C5AY00628G

Martins D, Levicky R, Songa Y-A. Enhancing the speed of morpholino-DNA biosensor by electrokinetic concentration of DNA in a microfluidic chip. Biosensors Bioelectronics.

Gao HL, Wang M, Wu ZQ, Wang C, Wang K, Xia XH. A morpholino-functionalized nanochannel-array for label-free SNPs detection. Anal Chem. 2015 Apr 7;87(7):3936-41. doi: 10.1021/ac504830e. Epub 2015 Mar 11

Hu W, Hu Q, Li L, Kong J, Zhang X. Detection of sequence-specific DNA with morpholino-functionalized silicon chip. Anal Methods. 2015;[Epub ahead of print] doi:10.1039/C4AY02780A

Zu Y, Tan M-H, Chowbay B, Lee SC, Yap H, Lee MT, Lu L-S, Chang C-P, Ying JY. Nanoprobe-based genetic testing. NanoToday. 2014;[Epub ahead of print] doi:10.1016/j.nantod.2014.04.003

Cao L, Zhao Y, Ji L-N, Zhang J, Wang K, Xia X-H. The Enhanced Enzymolysis Resistance of Surface-Immobilized DNA Caused by Hybridizing with Morpholino. Electroanalysis. 2013;[Epub ahead of print] doi:10.1002/elan.201200612

Schnell FJ, Crumley SL, Mourich DV, Iversen PL. Development of Novel Bioanalytical Methods to Determine the Effective Concentrations of Phosphorodiamidate Morpholino Oligomers in Tissues and Cells. BioResearch Open Access. 2013;[Epub ahead of print] doi:10.1089/biores.2012.0276.
In this paper, it is the Morpholino concentration being analyzed.

Gao Z, Deng H, Shen W, Ren Y. A Label-Free Biosensor for Electrochemical Detection of Femtomolar MicroRNAs. Anal Chem. 2013 Jan 16. [Epub ahead of print]

Qiao W, Kalachikov S, Liu Y, Levicky R. Charge-Neutral Morpholino Microarrays for Nucleic Acid Analysis. Anal Biochem. 2012;[Epub ahead of print] doi:10.1016/j.ab.2012.12.001

Zhao Y, Cao L, Ouyang J, Wang M, Wang K, Xia X. A Reversible Plasmonic Probe Sensitive for pH in Micro/nano-spaces Based on i-motif-modulated Morpholino-AuNPs Assembly. Anal Chem. 2012;[Epub ahead of print] doi:10.1021/ac302915a

Wang Y, Chen L, Liu X, Cheng D, Liu G, Liu Y, Dou S, Hnatowich DJ, Rusckowski M. Detection of Aspergillus fumigatus pulmonary fungal infections in mice with 99mTc-labeled MORF oligomers targeting ribosomal RNA. Nuclear Med Biol. 2012;[epub ahead of print] doi:10.1016/j.nucmedbio.2012.10.001.

Morpholinos as ISH probes for miRNA:
Lagendijk AK, Moulton JD, Bakkers J. Revealing details: whole mount microRNA in situ hybridization protocol for zebrafish embryos and adult tissues. Biology Open. 2012;[Advance Online Publication] doi:10.1242/bio.2012810

Liu Y, Irving D, Qiao W, Ge D, Levicky R. Kinetic Mechanisms in Morpholino-DNA Surface Hybridization. J. Am. Chem. Soc. 2011;[Epub ahead of print] DOI: 10.1021/ja202631b

Zu Y, Ting AL, Yi G, Gao Z. Sequence-Selective Recognition of Nucleic Acids under Extremely Low Salt Conditions by Using Nanoparticle Probes. Anal Chem. 2011;[Epub ahead of print] DOI: 10.1021/ac2001516

Liong M, Tassa C, Shaw SY, Lee H, Weissleder R. Multiplexed magnetic labeling amplification using oligonucleotide hybridization. Adv Mater. 2011 Sep 22;23(36):H254-7. doi: 10.1002/adma.201101401. Epub 2011 Jul 22. No abstract available.

O'Connor R, Tercero N, Qiao W, Levicky R. Electrochemical Studies of Morpholino-DNA Surface Hybridization. ECS Trans. 2011;(35)7:99-110. doi: 10.1149/1.3571981

Zu Y, Ting AL, Gao Z. Visualizing Low-Level Point Mutations: Enzyme-like Selectivity Offered by Nanoparticle Probes. Small. 2011 Feb 7;7(3):306-10. doi: 10.1002/smll.201001774. Epub 2010 Dec 22. No abstract available.

Liu G, Dou S, Liu Y, Liang M, Chen L, Cheng D, Greiner D, Rusckowski M, Hnatowich DJ. Unexpected side products in the conjugation of an amine-derivatized morpholino oligomer with p-isothiocyanate benzyl DTPA and their removal. Nucl Med Biol. 2011 Feb;38(2):159-63. Epub 2010 Oct 27.

Li SJ, Li J, Wang K, Wang C, Xu JJ, Chen HY, Xia XH, Huo Q. A Nanochannel Array-Based Electrochemical Device for Quantitative Label-free DNA Analysis. ACS Nano. 2010 Oct 19. [Epub ahead of print]

Cheng D, Wang Y, Liu X, Pretorius PH, Liang M, Rusckowski M, Hnatowich DJ. Comparison of (18)F PET and (99m)Tc SPECT Imaging in Phantoms and in Tumored Mice. Bioconjug Chem. 2010 Aug 18;21(8):1565-70

Tercero N, Wang K, Levicky R. Capacitive Monitoring of Morpholino-DNA Surface Hybridization: Experimental and Theoretical Analysis. Langmuir. 2010 Sep 7;26(17):14351-8.

Gong P, Wang K, Liu Y, Shepard K, Levicky R. Molecular Mechanisms in Morpholino-DNA Surface Hybridization. J Am Chem Soc. 2010 Jun 24. [Epub ahead of print]

Zhang GJ, Luo ZH, Huang MJ, Tay GK, Lim EJ. Morpholino-functionalized silicon nanowire biosensor for sequence-specific label-free detection of DNA. Biosens Bioelectron. 2010 Apr 9. [Epub ahead of print]

Tercero N, Wang K, Gong P, Levicky R. Morpholino Monolayers: Preparation and Label-free DNA Analysis by Surface Hybridization. J Am Chem Soc. 2009 Mar 18. [Epub ahead of print]

Wang X, Smirnov S. Label-Free DNA Sensor Based on Surface Charge Modulated Ionic Conductance. ACS Nano. 2009 Mar 13. [Epub ahead of print]

Gao Z, Boon PT. A DNA biosensor based on a morpholino oligomer coated indium-tin oxide electrode and a cationic redox polymer. Analyst. 2009; [Epub ahead of print]

Detecting labeled Morpholinos in tissues with an anti-fluorescein antibody:
Canto-Soler MV, Adler R. Optic cup and lens development requires Pax6 expression in the early optic vesicle during a narrow time window. Dev Biol. 2006 Jun 1;294(1):119-32. Epub 2006 Mar 27.

Wages JM Jr; Wages GM; Matthews P; Weller D; Summerton J. Affinity purification of RNA: sequence-specific capture by nonionic morpholino probes. Biotechniques. 1997 Dec;23(6):1116-21.