Nucleic acid-based aptamers: applications, development and clinical trials.
Short single-stranded oligonucleotides called aptamers, often termed as chemical antibodies, have been developed as powerful alternatives to traditional antibodies with respect to their obvious advantages like high specificity and affinity, longer shelf-life, easier manufacturing protocol, freedom to introduce chemical modifications for further improvement, etc. Reiterative selection process of aptamers over 10-15 cycles starting from a large initial pool of random nucleotide sequences renders them with high binding affinity, thereby making them extremely specific for their targets. Aptamer-based detection systems are well investigated and likely to displace primitive detection systems. Aptamer chimeras (combination of aptamers with another aptamer or biomacromolecule or chemical moiety) have the potential activity of both the parent molecules, and thus hold the capability to perform diverse functions at the same time. Owing to their extremely high specificity and lack of immunogenicity or pathogenicity, a number of other aptamers have recently entered clinical trials and have garnered favorable attention from pharmaceutical companies. Promising results from the clinical trials provide new hope to change the conventional style of therapy. Aptamers have attained high therapeutic relevance in a short time as compared to synthetic drugs and/or other modes of therapy. This review follows the various trends in aptamer technology including production, selection, modifications and success in clinical fields. It focusses largely on the various applications of aptamers which mainly depend upon their selection procedures. The review also sheds light on various modifications and chimerizations that have been implemented in order to improve the stability and functioning of the aptamers, including introduction of locked nucleic acids (LNAs). The application of various aptamers in detection systems has been discussed elaborately in order to stress on their role as efficient diagnostic agents. The key aspect of this review is focused on success of aptamers on the basis of their performance in clinical trials for various diseases.
Immunology & Cell Biology, Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), Deakin University, Geelong, Geelong Technology Precinct (GTP), Deakin University, Pigdons Road, Waurn Ponds, Geelong, Victoria 3217, Australia. jagat.kanwar@deakin.edu.au.
Jagat R
JR
Kanwar
Kislay
K
Roy
Nihal G
NG
Maremanda
Krishnakumar
K
Subramanian
Rakesh N
RN
Veedu
Raj
R
Bawa
Rupinder K
RK
Kanwar
D000818:Animals; D052157:Aptamers, Nucleotide / Q000737:chemistry* / Q000276:immunology / Q000627:therapeutic use*; D002469:Cell Separation; D002986:Clinical Trials as Topic; D006801:Humans; D057054:Molecular Imaging; D009696:Nucleic Acids / Q000737:chemistry*
D052157:Aptamers, Nucleotide; D009696:Nucleic Acids