7 Aptamers for Personalized Therapeutics
199
7.5 Future Perspective
Targeting proteins using aptamers is new domain with enormous opportunities in
diagnostics and therapeutics. Understanding aptamer structure, properties, and chemistry indicates significant advantages over current approaches in practice in medical
practice, since aptamers pose high thermo-stability, target specificity, and strong
affinity. Because aptamers are primarily oligonucleotides in nature, they demonstrate great variability in their secondary structures which confer diversity to the
aptamers. Unlike chemical drugs, even at high concentrations they do not show
immunogenicity and toxicity, and due to their small size, they can penetrate cell and
nucleus easily. Another exciting feature of these aptamer molecules is that they allow
chemical modifications in their structures by making use of modified nucleotides in
initial DNA/RNA libraries in the SELEX protocol. Chemical drug dock to the protein
targets efficiently but the toxicity has been a huge issue for decades in drug designing
and in vivo studies. In the same way aptamers form stable complexes with the target
proteins which has opened a new avenue in targeted therapies with lower chances of
side-effects.
In vitro and in vivo studies of aptamers have revealed promising efficacies as
well as safety profiles. Synthetic chemistry has efficiently tackled the primary challenges (stability and low molecular weight) of aptamer therapeutics. A number of
reported studies in peer-reviewed journals support the proficiencies of aptamers for
clinical trials of different diseases. Being target-specific, high affinity binders and
non-immunogenic aptamers present an incomparable prospect to make personalized
medicine a dream come true for more complex diseases. Although thousands of
new aptamers have been reported so far for a range of targets, a small number of
aptamers are in advance phases of approval for therapeutic use in patients. Principally with respect to the usage of aptamers in clinical trials, 43 clinical trials for
wide range of diseases have been listed in clinical trials database (https://clinicaltria
ls.gov), of which 21 have been completed till date. The diseases for which aptamers
are undergoing clinical trials include different cancers, age-related macular degeneration, HIV, Hippel-Lindau disease, diabetic macular edema, von Willebrand disease
type-2b, von Willebrand disease, arrhythmia atrial, atrial fibrillation, hypertension,
diabetes mellitus, small bowel Crohn’s disease, anemia, end-stage renal disease, etc.
Despite the current pace of development in this area, we believe that still there is a
lot to do in the field of aptamer structure, binding mechanisms, cross-reactivity, low
molecular weight, toxicity and so on. More collaborative and coordinated research
from molecular biologists, biochemists, biotechnologists, geneticists, bioinformaticians, synthetic biology and synthetic chemistry experts, structural biologists and
clinicians are needed at a sharp pace to sort out issues related to aptamers and their
application in translational medicine to revolutionize the way different diseases are
clinically diagnosed and treated in personalized medicine in near future.
199
7.5 Future Perspective
Targeting proteins using aptamers is new domain with enormous opportunities in
diagnostics and therapeutics. Understanding aptamer structure, properties, and chemistry indicates significant advantages over current approaches in practice in medical
practice, since aptamers pose high thermo-stability, target specificity, and strong
affinity. Because aptamers are primarily oligonucleotides in nature, they demonstrate great variability in their secondary structures which confer diversity to the
aptamers. Unlike chemical drugs, even at high concentrations they do not show
immunogenicity and toxicity, and due to their small size, they can penetrate cell and
nucleus easily. Another exciting feature of these aptamer molecules is that they allow
chemical modifications in their structures by making use of modified nucleotides in
initial DNA/RNA libraries in the SELEX protocol. Chemical drug dock to the protein
targets efficiently but the toxicity has been a huge issue for decades in drug designing
and in vivo studies. In the same way aptamers form stable complexes with the target
proteins which has opened a new avenue in targeted therapies with lower chances of
side-effects.
In vitro and in vivo studies of aptamers have revealed promising efficacies as
well as safety profiles. Synthetic chemistry has efficiently tackled the primary challenges (stability and low molecular weight) of aptamer therapeutics. A number of
reported studies in peer-reviewed journals support the proficiencies of aptamers for
clinical trials of different diseases. Being target-specific, high affinity binders and
non-immunogenic aptamers present an incomparable prospect to make personalized
medicine a dream come true for more complex diseases. Although thousands of
new aptamers have been reported so far for a range of targets, a small number of
aptamers are in advance phases of approval for therapeutic use in patients. Principally with respect to the usage of aptamers in clinical trials, 43 clinical trials for
wide range of diseases have been listed in clinical trials database (https://clinicaltria
ls.gov), of which 21 have been completed till date. The diseases for which aptamers
are undergoing clinical trials include different cancers, age-related macular degeneration, HIV, Hippel-Lindau disease, diabetic macular edema, von Willebrand disease
type-2b, von Willebrand disease, arrhythmia atrial, atrial fibrillation, hypertension,
diabetes mellitus, small bowel Crohn’s disease, anemia, end-stage renal disease, etc.
Despite the current pace of development in this area, we believe that still there is a
lot to do in the field of aptamer structure, binding mechanisms, cross-reactivity, low
molecular weight, toxicity and so on. More collaborative and coordinated research
from molecular biologists, biochemists, biotechnologists, geneticists, bioinformaticians, synthetic biology and synthetic chemistry experts, structural biologists and
clinicians are needed at a sharp pace to sort out issues related to aptamers and their
application in translational medicine to revolutionize the way different diseases are
clinically diagnosed and treated in personalized medicine in near future.