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Zebrafish contract research and commercial licenses

For contract research using Morpholinos in zebrafish or to license Morpholinos for commercial use in zebrafish in the USA, contact Zygogen, Inc. See the Outside Resources box for more information.

Gene Tools Online

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. Established delivery technologies it 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?
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. Now, with Vivo-Morpholinos, the specificity and efficacy of Morpholino oligos can be brought to experiments in adult animals. The list of over 3000 publications using Morpholinos is growing daily and is maintained on-line in a browseable database. Morpholino oligos have excellent antisense properties compared to other gene knockdown systems.

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.





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Links to Key Papers & Protocols

News

LSU's Oliver Wessely on microRNAs and Kidney Development.


NYU Poly: Postdoctoral Researcher Elevated to Highest IEEE Member Grade (current work: developing Morpholino biosensors)

Vivo-Morpholinos

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.

Vivo-Morpholinos in mice:
Vera T, Stec DE. Moderate Hyperbilirubinemia Improves Renal Hemodynamics in Angiotensin II Dependent Hypertension. Am J Physiol Regul Integr Comp Physiol. 2010 Jul 28. [Epub ahead of print]


Vivo-Morpholinos in the rat uterus:
Lecce L, Day M, Murphy CR. Abstract 15. ICAM-1 Is Involved in Uterine Receptivity in Rats. The Society for the Study of Reproduction 2010 Annual Meeting.


See our Vivo-Morpholinos page for more information and citations.

New Morpholino Papers

Double knockdowns altering fin structure:
Zhang J, Wagh P, Guay D, Sanchez-Pulido L, Padhi BK, Korzh V, Andrade-Navarro MA, Akimenko MA. Loss of fish actinotrichia proteins and the fin-to-limb transition. Nature. 2010 Jul 8;466(7303):234-7. Epub 2010 Jun 23.

Morpholino phenocopies mutant to confirm which gene is mutated:
Zhao X, Zhao L, Tian T, Zhang Y, Tong J, Zheng X, Meng A. Interruption of cenph causes mitotic failure and embryonic death and its haploinsufficiency suppresses cancer in zebrafish. J Biol Chem. 2010 Jun 23. [Epub ahead of print]


Knocking down a host factor inhibits viral replication in cultured cells:
Whitley DS, Yu K, Sample RC, Sinning A, Henegar J, Norcross E, Chinchar VG. Frog virus 3 ORF 53R, a putative myristoylated membrane protein, is essential for virus replication in vitro. Virology. 2010 Jul 13. [Epub ahead of print]


Does the small molecule inhibitor of a protein phenocopy the Morpholino knockdown?
Zhong H, Xin S, Zhao Y, Lu J, Li S, Gong J, Yang Z, Lin S. Genetic approach to evaluate specificity of small molecule drug candidates inhibiting PLK1 using zebrafish. Mol Biosyst. 2010 Aug;6(8):1463-8. Epub 2010 May 19.


Splice modifying Morpholinos in killifish:
Clark BW, Matson CW, Jung D, Di Giulio RT. AHR2 mediates cardiac teratogenesis of polycyclic aromatic hydrocarbons and PCB-126 in Atlantic killifish (Fundulus heteroclitus). Aquat Toxicol. 2010 Aug 15;99(2):232-40.


Morpholinos for nucleic acid capture at surfaces:
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]


Wen H, Linhoff MW, McGinley MJ, Li GL, Corson GM, Mandel G, Brehm P. Distinct roles for two synaptotagmin isoforms in synchronous and asynchronous transmitter release at zebrafish neuromuscular junction. Proc Natl Acad Sci U S A. 2010 Jul 19. [Epub ahead of print]


JoVE video on microinjecting zebrafish is now open access.


Morpholinos for treatment of potential biowarfare/bioterror agents:
There's no I in TMTI. CBRNe World. Summer 2010.


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Protocol updates

We now recommend storing Morpholino stock solutions at room temperature. Here is the updated Essential Information sheet.

Audio Notes (mp3)

Links to Audio Notes are on this page.

Sites and papers of interest

See the Outside Resources box for links to more papers and websites related to Morpholinos. Look in the right-hand column of the linked page.
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