Introduction
Aptamers were “discovered” in late 1989 and described in 1990 by Ellington and
Szostak and Tuerk and Gold. At that time a rather remarkable proposal was advanced:
single-stranded RNAs or DNAs had the capacity to fold into intricate structures
that might show strong similarities to the antigen-binding domains of antibodies.
Selection of such molecules—the aptamers—has been accomplished through iterative selections (SELEX) from vast (10
15 molecules) in libraries that are mixed with
targets. Those targets can be thought of as the antigens used in selections for antibodies. Today around 8,000 different proteins, largely human, have been used as
targets for identification of aptamers of one kind or another. Medical applications of
aptamers are approaching the markets swiftly.
We now understand, largely from Ron Breaker’s extraordinary work, that RNA
aptamers are a natural occurrence in biology. The discovery of aptamers and the
methods to identify them through SELEX are an example of experimental science
catching up with the evolution. Evolution had a time advantage over scientists, so
most things found in the lab exist in some biology, somewhere.
More than ten thousand aptamer papers were published over the last thirty years,
with almost a thousand patents sought and obtained. A minor industry was created
within biotech. The reasons are simple: in principle one can accomplish with aptamers
more or less what is possible with monoclonal antibodies, thus adding to therapeutic
monoclonal antibodies the alternative of synthetic aptamers made of short singlestranded RNAs or DNAs. Co-crystals of aptamer-target pairs show similar “fit” to
those observed in antibody-target pairs. The medical applications of aptamers were
anticipated immediately after the first aptamers were selected. That path was clear:
antibody uses were being developed in medicine and the aptamer scientists attempted
to do the same. A therapeutic aptamer—Macugen—was developed as an inhibitor
of VEGF, a protein that promotes angiogenesis; Macugen remains the only FDAapproved aptamer therapeutic, although that will change in the near future. At SomaLogic a protein profiling platform has been built and commercialized. That platform,
called SomaScan, quantifies the concentrations of 5,000 different human proteins
simultaneously, with high specificity and sensitivity. Aptamer medical applications
are coming.
ix
Aptamers were “discovered” in late 1989 and described in 1990 by Ellington and
Szostak and Tuerk and Gold. At that time a rather remarkable proposal was advanced:
single-stranded RNAs or DNAs had the capacity to fold into intricate structures
that might show strong similarities to the antigen-binding domains of antibodies.
Selection of such molecules—the aptamers—has been accomplished through iterative selections (SELEX) from vast (10
15 molecules) in libraries that are mixed with
targets. Those targets can be thought of as the antigens used in selections for antibodies. Today around 8,000 different proteins, largely human, have been used as
targets for identification of aptamers of one kind or another. Medical applications of
aptamers are approaching the markets swiftly.
We now understand, largely from Ron Breaker’s extraordinary work, that RNA
aptamers are a natural occurrence in biology. The discovery of aptamers and the
methods to identify them through SELEX are an example of experimental science
catching up with the evolution. Evolution had a time advantage over scientists, so
most things found in the lab exist in some biology, somewhere.
More than ten thousand aptamer papers were published over the last thirty years,
with almost a thousand patents sought and obtained. A minor industry was created
within biotech. The reasons are simple: in principle one can accomplish with aptamers
more or less what is possible with monoclonal antibodies, thus adding to therapeutic
monoclonal antibodies the alternative of synthetic aptamers made of short singlestranded RNAs or DNAs. Co-crystals of aptamer-target pairs show similar “fit” to
those observed in antibody-target pairs. The medical applications of aptamers were
anticipated immediately after the first aptamers were selected. That path was clear:
antibody uses were being developed in medicine and the aptamer scientists attempted
to do the same. A therapeutic aptamer—Macugen—was developed as an inhibitor
of VEGF, a protein that promotes angiogenesis; Macugen remains the only FDAapproved aptamer therapeutic, although that will change in the near future. At SomaLogic a protein profiling platform has been built and commercialized. That platform,
called SomaScan, quantifies the concentrations of 5,000 different human proteins
simultaneously, with high specificity and sensitivity. Aptamer medical applications
are coming.
ix