[Date Prev][Date Next][Thread Prev][Thread Next][Date Index][Thread Index]

[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

********************************************************
To unsubscribe from SANET-MG:
1- Visit http://lists.sare.org/archives/sanet-mg.html to unsubscribe or;
2- Send a message to <listserv@sare.org> from the address subscribed to the list. Type "unsubscribe sanet-mg" in the body of the message.

Visit the SANET-MG archives at: http://lists.sare.org/archives/sanet-mg.html
For more information on grants and other resources available through the SARE program, please visit http://www.sare.org.