Ok, so this is being considered by the FDA Center for Veterinary Medicine - Veterinary Medicine Advisory Committee. Basic information…took me less than a minute to find that out.
I'm skipping to the part about Aquadvantage salmon itself instead of all the background information, which is about the subject of genetically modifed animals at large and explains the agencies policies and procedures, etc.
Here is some of the briefing pack for the meeting, dated September 20, 2010
VMAC Briefing Packet: AquAdvantage Salmon
II. PRODUCT DEFINITION
FDA and Aqua Bounty Technologies, Inc. (ABT) agreed to a Product Definition for AquAdvantage Salmon containing information regarding product identity, the demonstrated claim for the product, and limitations for the use of AquAdvantage Salmon. That Product Definition follows:
Product Definition for AquAdvantage Salmon
Triploid hemizygous, all-female Atlantic salmon (Salmo salar) bearing a single copy of the α-form of the opAFP-GHc2 rDNA construct at the α-locus in the EO-1α lineage.
Significantly more of these Atlantic salmon grow to at least 100 g within 2700 deg C days than their comparators.
Limitations for Use
These Atlantic salmon are produced as eyed-eggs for grow-out only in the FDA-approved physically-contained fresh water culture facility.
III. MOLECULAR CHARACTERIZATION OF THE CONSTRUCT
Risk evaluation in the Molecular Characterization of the Construct step of the Hierarchical Review Process was essentially limited to characterizing the potential hazard(s) the rDNA construct might pose. In particular, we evaluated the intrinsic properties of the rDNA construct that might cause harm. The properties that were of most interest in this respect included potentially mobilizeable DNA sequences, or sequences encoding pathogens, toxins (including allergens), or substances likely to perturb the growth control of cells, tissues, or organs, except by explicit design. We also evaluated the purity of the construct in order to determine that unknown sequences were not introduced into the genetically engineered animals.
This evaluation was conducted in accordance with the approach later summarized in Guidance for Industry #187 Regulation of Genetically Engineered Animals Containing Heritable Recombinant DNA Constructs. As summarized in that document, typically, the information required for this section should include, but not be limited to, the following:
• a description of the source(s) of the various functional components of the construct;
• the sequence of the rDNA construct;
• the purpose of the modification;
• details of how the rDNA construct was assembled;
• the intended function(s) of the introduced DNA; and
• the purity of the preparation containing the rDNA construct prior to introduction into recipient animals or cells.
The evaluation of the Molecular Characterization of the Construct for AquAdvantage Salmon was organized in five general sections that address the characterization topics listed above.
1. Source and description of DNA for the inserted construct;
2. Construction, including method and intermediate organisms
3. Sequence of the final product.
4. Demonstration of promoter function in salmonid cells; and
5. Components of microinjection syringe
The available materials described construction and confirmation of a fish growth regulator (Chinook salmon growth hormone) under the control of transcriptional regulatory elements derived from ocean pout and Chinook salmon carried in a standard plasmid backbone. The constructs did not contain coding regions clearly derived from known toxins, pathogens, oncogenes, tumor suppressor genes, or sequences derived from transposable elements or retroviruses that would confer transgene mobilization. Thus, the evaluation of subsequent portions will focus on the Chinook salmon growth hormone gene and gene product, the ocean pout and Chinook salmon-derived regulatory sequences and the bacterial plasmid backbone.
We conclude that the data submitted are acceptable for the Molecular Characterization of the Construct portion of the hierarchical review of a new animal drug application for AquAdvantage Salmon.
1. Source and description of DNA
Although the plasmid portion of the rDNA construct is generally not intended to be inserted into the GE animal, an understanding of what plasmids were used to generate various intermediates in the assembly of the rDNA constructs was informative as to potential hazards associated with the plasmids as well as what rDNA to look for in subsequent steps.
Several closely related, and commonly used bacterial plasmids (pUC9, pUC13, pUC14 and pUC18) were used to generate various intermediates in the assembly of the rDNA construct used for generation of the AquAdvantage Salmon.
AquAdvantage Salmon were tested for pUC origin plasmid DNA sequences (see Molecular Characterization of the GE Animal Lineage, Section IV, below). No unanticipated sequences from these plasmids were found in the EO-1α lineage AquAdvantage Salmon.
b. Virus or Bacteriophage
No bacterial or eukaryotic viruses or sequences were used that would result in viruses or viral sequences being transferred to, or propagated in, the eventual GE animal.
Recombinant DNA inserts from three sources were used for the final construct. These sources included regulatory sequences from ocean pout, the growth hormone coding region from Chinook salmon and small synthetic linkers to aid in assembly of the inserts and plasmid. This final construction is discussed in detail below in section 2b.
i. Ocean Pout Anti-Freeze Protein (opAFP) Regulatory Sequences
The upstream (5’) and downstream (3’) regulatory sequences used in the construct were obtained from a genomic isolate of a Type III anti-freeze protein (AFP) gene from the ocean pout (op). Isolation of the opAFP gene is available in J. Biol. Chem., vol. 263(24)12049-12055 (Hew et al., 1988). More information regarding the isolation of the opAFP regulatory regions can be found in Mol. Marine Biol. Biotech., vol. 1(4/5)290-300 (Du et al., 1992b).
ii. Chinook Salmon Growth Hormone (GH) Coding Sequence
The Chinook salmon GH gene was identified and isolated from a cDNA library prepared using pituitary gland of Chinook salmon. This cDNA is full-length and encodes a single, mature hormone.
iii. Synthetic linkers
Two synthetic DNAs corresponding to the 5’ untranslated regions (UTRs) were prepared using established sequences of the Chinook salmon GH-1 and the ocean pout AFP. These dsDNA strands included 5’ Bgl II and 3’ Pst I sites, giving rise to 75 bp and 74 bp 5’ UTRs, respectively. The GH-1 UTR was used for assembly of the opAFP-GHc construct, whereas the AFP UTR was used for the opAFP-GHc2 construct. This difference in 5’ UTR constitutes the only reported difference between opAFP-GHc and opAFP-GHc2.
Conclusion: The submitted materials described a standard plasmid backbone, transcriptional regulatory elements derived from ocean pout, a fish protein growth regulator (Chinook salmon growth hormone), and synthetic primers. The material provided in the submissions did not suggest that there were any sequence elements in the constructs that contained coding regions clearly derived from known toxins, pathogens, oncogenes, tumor suppressor genes, or sequences derived from transposable elements or retroviruses that would confer transgene mobilization. Thus, the evaluation will focus on the Chinook salmon growth hormone gene and gene product, the ocean pout and Chinook salmon-derived regulatory sequences and the bacterial plasmid backbone.