AMP > Discussion > AMPs and  biotechnology: Is there a promising future?

Good progress has been achieved with respect to defining the rules by which the immune system works and its complexity and interconnections are being slowly understood. In this perspective, the innate immune response has been neglected, but the consolidation of new discoveries in the field is slowly repositioning it (Fearon, 2000; Nathan, 2002). Nonetheless, the potential massive use of these natural compounds is hampered by the limited amount  that can be extracted in vivo as well as non-optimal specific activities, which would require huge amounts for clinical and therapeutical application. This is the point where biotechnology should play a pivotal role in the near future, independent that chemical synthesis of peptides could also be a non exclusive alternative. Classically, these peptides are encoded by small genes, with conserved sequences and patterns that make their cloning easy, and should allow easy expression and both small- and large scale purification . From a more innovative point of view, gene amplification and transgenesis seem like feasible ways to increase production and enhance specific activity of selected molecules. But, is this possible to achieve in vivo? The answer is, once again, yes. Biosynthetic and preparative production of AMPs have been successfully reported, as have synthetic forms of AMP analogues displaying enhanced antimicrobial activity( Cudic et al. 2003). There are some additional examples: Since AMPs were first characterized in insects, a great deal of complementary work comes from that area of applied research. One of the most notable pieces of work deals with Drosophila mutants not expressing any known endogenous AMP genes and, as a consequence, highly susceptible to bacterial infections. Genetic manipulation of these mutants complemented with a single constitutively expressed AMP gene can rescue susceptibility to infections  . In plants, as expected, tobacco has been thetarget for successful engineered-production of mammalian AMPs  , as well as amphibian anti microbial peptides, where vertical transmission of resistance occurs . In addition,  AMPs from  other origins have been added to confer disease resistance in transgenic tobacco and banana  and potato(Osuky et al. 2000), , thus opening unsuspected alternatives to provide agronomically relevant levels of disease control worldwide .


References

FEARON, D.T. Innate immunity-beginning to fulfil its promise? Nature Immunology, 2000, vol. 2, p. 102 -103.

NATHAN, C. Catalytic antibody bridges innate and adaptive immunity. Science, 2002, vol. 298, no. 5601, p. 2143-2144.

CUDIC, M.; CONDIE, B.A.; WEINER, D.J.; LYSENKO, E.S.; XIANG, Z.Q.; INSUG, O.; BULET, P. and OTVOS, JR. L. Development of novel antibacterial peptides that kill resistant isolates. Peptides, vol. 24. In press, 2003.

OSUKY, M.; ZHOU, G.; OSUSKA, L.; HANCOCK, R.E.W.; KAY, W.W. and MISRA, S. Transgenic plants expressing cationic peptide chimeras exibit broad-spectrum resistance to phytopathogens. Nature Biotechnology, 2000, vol. 18, no. 11, p. 1162-1166.




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