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Updated: Aug 18, 2026
Microinjection of mRNA and Morpholino Antisense Oligonucleotides in Zebrafish Embryos.
Published on: May 7, 2009
Manipulation of zebrafish embryogenesis by phosphorodiamidate morpholino oligomers indicates minimal non-specific
Patrick L Iversen1, Scott Newbry
1AVI BioPharma Inc, 4575 SW Research Way, Corvallis, OR 97333, USA. piversen@avibio.com
Abstract:
The incidence of teratogenicity caused by therapeutic agents is a significant concern in drug development. Approaches to screening active agents in drug development tend to be limited by relevance to humans, cost from the large number of animals required for testing and complicated by barriers to drug entry into the test organism. The era post-human, -mouse and -zebrafish genome sequence determination should result in more precise experimental approaches to the evaluation of teratogenic potential. Peer-reviewed publications (204 papers) from independent investigators evaluating phosphorodiamidate morpholino oligomers (PMOs) in functional genomic studies are reviewed. These studies utilized over 47,000 embryos and resulted in 0.3% off-targeted or potential teratogenic effects, while at the same time producing the 74% phenotypic penetrance expected for the targeted gene. This represents a very compelling case for the minimal teratogenic potential of PMO chemistry.
Insights
Phosphorodiamidate morpholino oligomers (PMOs) show minimal teratogenic potential in drug development screening. Extensive studies on over 47,000 embryos confirm their safety and efficacy in functional genomics.
Area of Science:
- Drug Development
- Developmental Toxicology
- Functional Genomics
Background:
- Teratogenicity from therapeutic agents is a major concern in drug development.
- Current screening methods face limitations in human relevance, cost, and organismal drug entry.
- Genomic advancements enable more precise teratogenicity evaluations.
Purpose of the Study:
- To evaluate the teratogenic potential of phosphorodiamidate morpholino oligomers (PMOs).
- To assess the safety and efficacy of PMOs in functional genomic studies.
Main Methods:
- Review of 204 peer-reviewed publications on PMO use in functional genomics.
- Analysis of studies involving over 47,000 embryos.
- Evaluation of off-targeted effects and phenotypic penetrance.
Main Results:
- PMO studies reported only 0.3% off-targeted or potential teratogenic effects.
- Phenotypic penetrance for targeted genes was 74%, as expected.
- Demonstrated minimal teratogenic potential of PMO chemistry.
Conclusions:
- PMOs exhibit a very low incidence of teratogenicity.
- PMOs are a safe and effective tool for functional genomic studies.
- PMO chemistry presents a compelling option for drug development screening.
