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[SANET-MG] Human gene products in the micro alga Chlamydomonas reinhardii
“Human gene products in the micro alga Chlamydomonas reinhardii :
proceed with caution”
Professor Joe Cummins
Professor Emeritus of Genetics University of Western Ontario
London, Ontario, Canada N6C4Z9
Telephone 519 681 5477
e-mail:jcummins@uwo.ca
I understand that Rincon Pharmaceuticals and Mera Pharmaceuticals
who will be testing and producing on a 4 acre ocean front piece of land
in Kona a genetically engineered alga Chlamydomonas reinhardii
.engineered with human monoclonal
antibodies and marker genes. A full review of that proposal has not been
available so I am basing my comments on the scientific publications and
my understanding that the modified algae will be cultivated in large
plastic tubes located in an open environment on a surface covered with
gravel sitting atop the soil. My primary reservation about the project
is that Chlamydomonas reinhardii is well known to be a soil microbe as
well as growing in freshwater. Once established in the soil the microbe
may be capable of secreting human antibodies capable of polluting
groundwater and exerting untested impact on the soil ecology.
Transgenic microalgae as green cell factories for producing
pharmaceuticals and food additives. Either chromosomal or chloroplast
transgenes can be produced with ease and a number of transgenic algae
have been prepared. Chlamydomonas reinhardii is a preferred organism
for such experiments because its genome has been sequenced and it has a
long history of laboratory culture One technical drawback with the alga
is codon bias related to the high GC content in the algal DNA, To
achieve significant production the code of human and many other genes
must be altered to fit the bias of the algal cell, For that reason the
human pharmaceutical products are produced from synthetic approximations
of the human gene(1). The synthetic human DNA in the alga should not be
deemed equivalent until it has been tested for untoward effects on
humans and the environmental biota.
Mayfield and Franklin described construction of transgenic
Chlamydomonas reinhardii whose chloroplasts had been modified for
expression of human antibodies. The human genes were synthetic
approximation extensively adjusted for codon bias. Either the rbcl
promoter (ribulose-1,5-bisphosphate carboxylase of the chloroplast) or
the atpA promoter (alpha -subunit of the chloroplast ATP synthase of
the chloroplast) were used to drive the antibody gene. The rbcL
transcription terminator followed the human gene. A 16s (small)
ribosomal subunit with resistance to the antibiotic accompanied the
human gene transformation(2). IgA antibody directed against herpes
simplex virus were produced in Chlamydomonas reinhardii (3). Single
chain antibodies agains the herpes svirus were produced in Chlamydomonas
reinhardii (4).
Production of transgenic antibodies provides valuable
pharmaceutical products useful in both therapy and diagnosis. However,
the human antibodies will certain serve as antigens in humans or mammals
of diverse origin and repeated exposure to the antibodies is likely to
result in anaphylaxis which can cause death. For that reason great care
must be exerted in insuring that the transgenic algae do not establish a
niche in the ecology of the Island by carelessness or through typhoons
or tsunami.
Release of the transgenic Chlamydomonas reinhardii to soil or
freshwater could establish colonies of the alga in the soil The alga
is equipped to swim in water using flagella and to glide over the
surface of soil particles after modifying the flagella (5). That alga is
a notable member of the soil microbial flora. A related Chlamydomonas
has been observed to be important in soil aggregate stabilization (6).
In conclusion, it seems clear that a large number of pilot
experiments should be completed to ensure that the humanized
Chlamydomonas reinhardii are produced in an area where they may creates
disastrous pollution.
Refernces
1. Leon-Banares R, Gonzalez-Ballester D, Galvan A. and Fernandez E.
Transgenic microalgae as green cell-factories. Trends Biotechnol. 2004
Jan;22(1):45-52
2. Mayfield,S. and Franklin,S. Expression of human antibodies in
eukaryotic micro-algae Vaccine 2005 ,23,1828-32
3. Franklin S and Mayfield S . Recent developments in the production
of human therapeutic proteins in eukaryotic algae. Expert Opin Biol
Ther. 2005 Feb;5(2):225-35
4. Mayfield SP, Franklin SE and Lerner RA. Expression and assembly
of a fully active antibody in algae. Proc Natl Acad Sci U S A. 2003 Jan
21;100(2):438-42
5. Mitchell B, Grulich L and Mader M Flagellar quiescence in
Chlamydomonas: Characterization and defective quiescence in cells
carrying sup-pf-1 and sup-pf-2 outer dynein arm mutations. Cell Motil
Cytoskeleton. 2004 Mar;57(3):186-96
6. Metting,B. Population dynamics of Chlamydomonas sajao and its
influence on soil aggregate stabilization in the field Applied and
Environmental Microbiology 1986 51, 1161-4
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