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Morpholino Publications Database
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What Do We Make?Gene Tools makes Morpholino antisense oligos. We are the sole commercial manufacturer selling research quantities of Morpholinos world-wide. Morpholino oligos can knockdown gene expression, modify splicing or inhibit miRNA activity and maturation. Morpholinos are the premier knockdown tools used in developmental biology labs, the best RNA-blocking reagents for cells in culture and, as Vivo-Morpholinos, the most specific knockdown technology available for other animal models.
Morpholino oligos are short chains of about 25 Morpholino subunits. Each subunit is comprised of a nucleic acid base, a morpholine ring and a non-ionic phosphorodiamidate intersubunit linkage. Morpholinos do not degrade their RNA targets, but instead act via an RNAse H-independent steric blocking mechanism. With their requirement for greater complementarity with their target RNAs, Morpholinos are free of the widespread off-target expression modulation typical of knockdowns which rely on RISC or RNase-H activity. They are completely stable in cells and do not induce immune responses.
With their high mRNA binding affinity and exquisite specificity, Morpholinos yield reliable and predictable results. Depending on the oligo sequence selected, they either can block translation initiation in the cytosol (by targeting the 5' UTR through the first 25 bases of coding sequence), can modify pre-mRNA splicing in the nucleus (by targeting splice junctions or splice regulatory sites) or can inhibit miRNA maturation and activity (by targeting mature miRNA or pri-miRNA), as well as more exotic applications such as ribozyme inhibition or translational frameshifting. Morpholinos have been shown effective in animals, protists, plants and bacteria.
We are continually developing novel cytosolic delivery systems like our 'Endo-Porter' for cultured cells and our Vivo-Morpholinos for in vivo delivery. With established delivery technologies it's easy to deliver Morpholinos into cultures, embryos or animals -- making Morpholinos the best tools for genetic studies and drug target validation programs.
What Sets Us Apart?Morpholino oligos have excellent antisense properties compared to other gene knockdown systems. Microinjection or electroporation of Morpholino oligos into the embryos of frogs, zebrafish, chicks, sea urchins and other organisms successfully and specifically shuts down the expression of targeted genes, making Morpholinos an indispensable tool of developmental biologists. Morpholinos have also proven their versatility and efficacy in cultures of primary and immortal cells when delivered by Endo-Porter or electroporation. Vivo-Morpholinos bring the specificity and efficacy of Morpholino oligos to experiments in adult animals. The list of over 5000 publications using Morpholinos is growing daily and is maintained on-line in a browseable database.
Besides providing the best knockdown and splice modification tools, we also provide the best customer support available in the gene silencing industry. Our customer support team includes three scientifically active Ph.D.-level scientists who are available to: 1) discuss your experiment design, 2) design your oligos for you, and 3) help you troubleshoot your experiments, all at no additional cost.
What Are Our Long-Term Goals?Gene Tools is a research-based company led by Dr. Jim Summerton (inventor of Morpholino oligos). While providing Morpholino oligos to researchers world-wide, Gene Tools continues to develop methods to improve in vivo delivery, in particular systemic in vivo delivery of therapeutically useful concentrations of Morpholinos into the cytosol of cells in adult organisms. Our research into in vivo delivery has led us to new molecules which are potentially useful for diagnostic and therapeutic applications in cancer; these are still in development.
Key Papers, Protocols & Citations
The EU lists Morpholino phosphorodiamidate oligos among substances used for research to be relieved from EU import duties.
New Morpholino Papers
Papanayotou C, De Almeida I, Liao P, Oliveira NM, Lu SQ, Kougioumtzidou E, Zhu L, Shaw A, Sheng G, Streit A, Yu D, Wah Soong T, Stern CD. Calfacilitin is a calcium channel modulator essential for initiation of neural plate development. Nat Commun. 2013;4:1837. doi: 10.1038/ncomms2864.
Margolin DH, Kousi M, Chan Y-M, Lim ET, Schmahmann JD, Hadjivassiliou M, Hall JE, Adam I, Dwyer A, Plummer L, Aldrin SV, O’Rourke J, Kirby A, Lage K, Milunsky A, Milunsky JM, Chan J, Hedley-Whyte ET, Daly MJ, Katsanis N, Seminara SB. Ataxia, Dementia, and Hypogonadotropism Caused by Disordered Ubiquitination. N Engl J Med. 2013;[Epub ahead of print] doi:10.1056/NEJMoa1215993 ********************************* More Morpholino citations are here.
Gene Tools offers custom-sequence Vivo-Morpholinos. Vivo-Morpholinos are Morpholino oligos with delivery moieties attached, enabling the oligos to enter cells in adult animals. Vivo-Morpholinos can be used for iv, ip, or local injections, icv infusions and cell cultures.
Martin NT, Nakamura K, Davies R, Nahas SA, Brown C, Tunuguntla R, Gatti RA, Hu H. ATM-Dependent MiR-335 Targets CtIP and Modulates the DNA Damage Response. PLoS Genet. 2013;9(5):e1003505. doi:10.1371/journal.pgen.1003505
miRNA knockdown in cultured cells
Jacobi CLJ, Rudigier LJ, Scholz H, Kirschner KM. Transcriptional regulation by the Wilms tumor protein, Wt1, suggests a role of the metalloproteinase Adamts16 in murine genitourinary development. J Biol Chem. 2013;[Epub ahead of print] doi:10.1074/jbc.M113.464644
Murine organotypic cultures: kidney and gonads
See our Vivo-Morpholinos page for more information and citations.
Gene Tools now offers custom-sequence Photo-Morpholinos. A Photo-Morpholino is a Morpholino oligo with a photo-cleavable linkage in the middle. Photo-Morpholinos can be cleaved by 365nm light. Gene Tools also manufactures a lightbox for cleaving Photo-Morpholinos.
Saxena A, Peng BN, Bronner ME. Sox10-dependent neural crest origin of olfactory microvillous neurons in zebrafish. eLife. 2013;2:e00336 doi:10.7554/eLife.00336 Eisenhoffer GT, Loftus PD, Yoshigi M, Otsuna H, Chien CB, Morcos PA, Rosenblatt J. Crowding induces live cell extrusion to maintain homeostatic cell numbers in epithelia. Nature. 2012 Apr 15;484(7395):546-9. doi: 10.1038/nature10999. See our Photo-Morpholinos page for more information and citations.
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