Exploring the CRISPR revolution in aquatic species and its implications for food security, conservation, and scientific discovery
Imagine if we could help fish resist devastating infections without antibiotics, or help endangered species adapt to warming oceans. What if we could understand exactly why some fish populations collapse while others thrive? These are no longer hypothetical questions in marine biology—they're becoming tangible realities through genome editing technology.
At the intersection of conservation, aquaculture, and basic science, researchers are using molecular tools to rewrite the very blueprint of aquatic life, creating new possibilities for sustainable food production and species preservation.
The global demand for fish has doubled since the 1990s, with aquaculture now producing more biomass than global beef production 9 . Meanwhile, climate change and human activities have left measurable marks on fish DNA—Eastern Baltic cod have not only become scarcer but genetically programmed to grow more slowly due to intensive fishing pressure . In this complex landscape, gene editing technologies like CRISPR-Cas9 are emerging as powerful tools that could help address challenges ranging from disease outbreaks in fish farms to the genetic rescue of vulnerable species.
At its core, CRISPR-Cas9 is a precise genetic modification system adapted from a natural defense mechanism in bacteria. The system consists of two key components: the Cas9 enzyme that acts as "molecular scissors" to cut DNA, and a guide RNA that directs these scissors to a specific genetic address in the genome 1 .
When CRISPR-Cas9 creates a cut in the DNA, the cell's natural repair mechanisms kick in. The most common repair pathway—non-homologous end joining (NHEJ)—often results in small insertions or deletions that disrupt gene function, creating knockouts 5 7 . For more precise edits, researchers can provide a DNA template that the cell uses to repair the break through homology-directed repair (HDR), allowing for specific genetic changes 7 .
Base editors: These tools enable single-letter changes in the genetic code without cutting both strands of DNA. Cytosine base editors convert C•G to T•A base pairs, while adenine base editors convert A•T to G•C base pairs 6 .
Prime editors: Considered "search-and-replace" tools for DNA, these systems can insert, delete, or combine all possible base-to-base conversions without double-strand breaks 2 .
| Technology | Mechanism | Precision | Primary Applications in Fish |
|---|---|---|---|
| CRISPR-Cas9 | Creates double-strand breaks in DNA | Moderate | Gene knockouts, disease resistance studies |
| Base editors | Chemically converts one DNA base to another | High | Modeling human genetic diseases, introducing specific traits |
| Prime editors | Uses reverse transcriptase to copy edited sequences | Very high | Precise nucleotide substitutions, short insertions |
| TALENs | Protein-guided DNA cutting | Moderate | Targeted mutagenesis before CRISPR |
| ZFNs | Protein-guided DNA cutting | Moderate | Early targeted gene editing |
Disease outbreaks represent a major challenge for global aquaculture, causing significant economic losses and threatening food security 1 . Conventional disease control strategies—antibiotics, vaccines, and selective breeding—have achieved varying levels of success but are often limited by effectiveness, cost, and environmental concerns 1 9 . CRISPR-based approaches offer a promising alternative by targeting both the host's susceptibility genes and the pathogens themselves.
Researchers are using CRISPR to identify and modify genes that influence disease susceptibility in fish.
CRISPR systems are also being deployed against the pathogens themselves.
| Species | Target Gene | Pathogen/Disease | Outcome |
|---|---|---|---|
| Channel catfish | Myostatin (mstn) | Edwardsiella ictaluri (bacteria) | Enhanced growth and improved resistance |
| Zebrafish | tnf-α1 | Edwardsiella piscicida (bacteria) | Reduced disease resistance (identified critical immune gene) |
| Various species | Multiple immune genes | Viral hemorrhagic septicemia virus | Identified key resistance pathways |
| Crustaceans | Chitinase | Bacterial infection | Altered immune response |
A landmark 2025 study published in eLife provides a compelling example of how precision genome editing is advancing fish research 2 . Researchers at the University of Exeter and AstraZeneca compared two prime editing systems—PE2 (nickase-based) and PEn (nuclease-based)—for their ability to make precise genetic changes in zebrafish.
Researchers designed specialized guide RNAs called pegRNAs that contained both targeting sequences and templates for the desired edits.
At the one-cell stage, zebrafish embryos were injected with mixtures of Prime Editor proteins and synthetic pegRNAs.
Injected embryos were incubated at 32°C to enhance editing efficiency.
At 96 hours post-fertilization, genomic DNA was extracted and analyzed using amplicon sequencing and T7 endonuclease I assays to quantify editing success.
Edited fish were raised to adulthood and bred to determine if genetic changes could be inherited.
| Editing Goal | Editor System | Efficiency | Key Findings |
|---|---|---|---|
| Nucleotide substitution in crbn gene | PE2 (nickase) | 8.4% | Higher precision, fewer indels |
| Nucleotide substitution in crbn gene | PEn (nuclease) | 4.4% | More indels, lower precision score |
| 3bp stop codon insertion in ror2 gene | PEn/pegRNA | High | Effective protein truncation |
| 3bp stop codon insertion in ror2 gene | PE2/pegRNA | Low | Less effective for insertions |
Results and Significance: The study revealed that PE2 was more effective for single nucleotide substitutions, achieving precise base changes in 8.4% of cases compared to 4.4% with PEn 2 . However, PEn excelled at inserting short DNA sequences (3-30 base pairs), such as stop codons that truncate proteins. These modifications were not only efficient but heritable—edited fish passed the genetic changes to their offspring 2 .
| Reagent/Tool | Function | Example Applications in Fish |
|---|---|---|
| Cas9 protein | Creates double-strand breaks in DNA at target locations | Gene knockout in zebrafish and commercial fish species |
| Guide RNA (gRNA) | Directs Cas9 to specific genomic sequences | Targeting growth, disease resistance, or reproduction genes |
| Base editors (CBEs, ABEs) | Enables single-nucleotide changes without double-strand breaks | Modeling human genetic diseases in zebrafish |
| Prime editors | Allows precise insertions, deletions, and base substitutions | Creating specific disease models in zebrafish |
| Ribonucleoprotein (RNP) complexes | Pre-assembled Cas9-gRNA complexes for direct delivery | Reducing off-target effects in zebrafish embryos |
| pegRNA | Specialized guide RNA for prime editing containing reverse transcriptase template | Precise sequence insertion in zebrafish genomes |
| Microinjection apparatus | Delivers editing components into fertilized eggs | Introducing CRISPR components into zebrafish embryos |
As gene editing technologies continue to advance, their applications in fish biology and aquaculture are expanding in exciting directions:
Researchers are exploring how gene editing might help fish adapt to changing ocean conditions. Historical genomic studies have revealed that some tropical fish species in the Philippines have lost significant genetic diversity—as much as 4% in cardinal fish populations near urban areas—while others have evolved rapidly in response to pollution and warming seas 4 .
The unexpected preservation of century-old fish DNA has created unique opportunities for what researchers call "genomic time travel" 4 . By comparing historical DNA with modern samples, scientists can identify genetic changes that have occurred in response to human activities, providing valuable baselines for conservation efforts.
The power to rewrite the genetic code of aquatic species comes with significant responsibility. Important considerations include environmental impacts, genetic diversity concerns, and the need for robust regulatory frameworks to ensure responsible development and deployment of these technologies 1 9 .
Genome editing in fish represents a powerful convergence of basic science and applied technology—a tool that is transforming everything from how we model human diseases to how we produce sustainable seafood. While the CRISPR revolution in fish research began with simple gene knockouts, it has rapidly evolved to include precision editing that can change single genetic letters with remarkable accuracy.
The journey ahead requires careful navigation—balancing the tremendous potential of these technologies with thoughtful consideration of their ecological and ethical implications. As research continues to advance, the dialogue between scientists, policymakers, and the public will be essential to ensure that genetic technologies are developed and deployed responsibly. In an era of growing environmental challenges and increasing global food demands, the ability to understand and carefully modify the genetic blueprint of fish species may become an increasingly important part of creating a sustainable future for both our food systems and aquatic ecosystems.