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