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Notification report


General information

Notification Number
B/FR/05/02/01

Member State to which the notification was sent
France

Date of acknowledgement from the Member State Competent Authority
06/01/2005

Title of the Project
Pluriannuals field experimentations of genetically modified corn expressing a gastric lipase for medical uses.

Proposed period of release:
01/04/2005 to 31/10/2008

Name of the Institute(s) or Company(ies)
Meristem Therapeutics, ;


3. Is the same GMPt release planned elsewhere in the Community?
No

Has the same GMPt been notified elsewhere by the same notifier?
Yes

If yes, notification number(s):
B/FR/00/02/07;

Genetically modified plant

Complete name of the recipient or parental plant(s)
Common NameFamily NameGenusSpeciesSubspeciesCultivar/breeding line
maizepoaceaezeazea maysmays- hybrid seeds with cytoplasmic male sterility - parental male lines (male fertile, non restorer) - parental female lines (male sterile and male fertile, non restorer)

2. Description of the traits and characteristics which have been introduced or modified, including marker genes and previous modifications:
The genes introduced confer to the maize:
- Ability to produce a gastric lipase in seeds
- Tolerance to glufosinate
There have been no previous genetic modifications of the parental organism


Genetic modification

3. Type of genetic modification:
Insertion;

In case of insertion of genetic material, give the source and intended function of each constituent fragment of the region to be inserted:
A binary plasmid which was introduced in a disarmed Agrobacterium strain has been used. The vector contains :
- a gene fusion between the signal peptide sequence from a rabbit protein precursor and a sequence that encodes a dog gastric lipase (seed specific expression). This enzyme catalyses the hydrolysis of alimentary long-chain triglycerides in vivo
- the bar coding sequence from Streptomyces hygroscopicus. This gene used as a selective marker confers tolerance to glufosinate ammonium (constitutive expression).


6. Brief description of the method used for the genetic modification:
The method used is the biologic transformation by Agrobacterium tumefaciens.

7. If the recipient or parental plant is a forest tree species, describe ways and extent of dissemination and specific factors affecting dissemination:
Not applicable

Experimental Release

1. Purpose of the release:
Previous field experimentations have allowed the extraction and purification of recombinant lipase from corn. This recombinant gastric lipase has been used to realize toxicological studies carried out on animals, clinical studies phase I carried out on healthy volunteers (men and women) and clinical studies phase IIa carried out on patients reached by cystic fibrosis. These studies showed:
- no toxicity of the gastric lipase ingested in great quantity,
- a good tolerance of the gastric lipase in single and repeated oral administration,
- a significant improvement of the absorption of the lipids for the sick subjects.

The goal of these releases is to produce enough grains producing gastric lipase in order to:
o finish the clinical studies necessary to obtaining the marketing authorization with the purified recombining lipase produced,
o realize galenic studies,
o test the process of extraction and purification of the gastric lipase at pre-industrial scale,
o develop new maize hybrids to be able to diversify the area of cultivation,
o optimize our know how on Plant Made Pharmaceutical production in order to reach regulatory requirements applicable to the obtention of active ingredients for therapeutic uses.


2. Geographical location of the site:
In 2005 the releases are planned in the center of France (Puy de Dôme, Auvergne).

3. Size of the site (m2):
Puy de Dôme: 211 000 m2 shared on 6 sites (including non transgenic border rows, and non transgenic maize used as pollinators for biomass production plots).

4. Relevant data regarding previous releases carried out with the same GM-plant, if any, specifically related to the potential environmental and human health impacts from the release:
Field experimentations were already conducted in several locations in France and abroad with the same event of transformation. These field experimentations (productions of seeds and biomass) were carried out during the years 2000, 2001, 2002 and 2003 on field from a few hundreds of square meters to around ten hectares and no environmental problems were reported for these trials.

The handling of the GMPts is daily; since many years many people are in contact with these GMPts whatever the environment : laboratory, greenhouse, field, pilot unit and, up to today, nobody noted to have a problem of health and in particular an allergy of contact.


Environmental Impact and Risk Management

Summary of the potential environmental impact from the release of the GMPts:
Introduced traits do not modify the plant persistency in the environment, the ability to survive, the capacities of dissemination. Even if these GMPts are tolerant to the glufosinate ammonium, this benefit of selection can’t be maintained in French agro systems because of the non use of glufosinate ammonium on commercial crops. Without pression of selection, the selective advantage cannot be maintained.
No selective advantage is conferred by the expression of a gastric lipase in seeds of GMPts.
There is no wild species sexually compatible with maize in Europe so potential interspecific crossings are not possible in these sites. The only potential crossing can be between GMPts and conventional maize. However this type of crossing is very improbable due to the fact that measures are taken for the control of non intentional release in the environment and pollen dissemination (Cf. paragraph E).
In previous experiments, there was no direct or indirect negative or positive impact observed on non-target organisms. Moreover, the whole of the toxicological studies carried out on animals and clinical studies carried out on humans have not showed any toxicity of the gastric lipase.
Except the specific cultivation management, the techniques of cultivation used are the same ones as those usually used for conventional maize production. So no supplemental effect is expected for environment.
To our knowledge, no risks to human and animal health or the environment from the deliberate release of genetically modified maize expressing a gastric lipase and tolerant to glufosinate ammonium herbicide have been reported.


Brief description of any measures taken for the management of risks:
- For biomass production (transgenic plants are male sterile or detasseled), a 200 meters isolation distance will be maintained to any other commercial corn crop. For seeds production, a 400 meters isolation distance will be maintained to any other commercial corn crop.
- At least 4 border rows of non transgenic maize will be sown all around each experimental field.
- Use of a cytoplasmic male sterility system for the production of biomass.
- Destruction by crushing of the residues of culture at the end of the harvest.
- Monitoring of possible volunteers during one year after harvest.
- No commercial corn culture will be established on these experimental fields the following year.
- Maize will not be used for feed or food.

The regular follow-up of the trials makes it possible to identify in an early way any event or development which is not desirable. Thus the trials can be stopped quickly by the classic means of destruction (chemical treatment with a conventional total herbicide other than the glufosinate ammonium or mechanical treatment with crusher for example).


Summary of foreseen field trial studies focused to gain new data on environmental and human health impact from the release:
Not applicable

Final report
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European Commission administrative information

Consent given by the Member State Competent Authority:
Yes
27/04/2005 00:00:00
Remarks: