Nucleic Acid Aptamers: Clinical Applications and Promising New Horizons

Abstract

Aptamers are a special class of nucleic acid molecules that are beginning to be investigated for clinical use. These small RNA/DNA molecules can form secondary and tertiary structures capable of specifically binding proteins or other cellular targets; they are essentially a chemical equivalent of antibodies. Aptamers have the advantage of being highly specific, relatively small in size, and non-immunogenic. Since the discovery of aptamers in the early 1990s, great efforts have been made to make them clinically relevant for diseases like cancer, HIV, and macular degeneration. In the last two decades, many aptamers have been clinically developed as inhibitors for targets such as vascular endothelial growth factor (VEGF) and thrombin. The first aptamer based therapeutic was FDA approved in 2004 for the treatment of age-related macular degeneration and several other aptamers are currently being evaluated in clinical trials. With advances in targeted-therapy, imaging, and nanotechnology, aptamers are readily considered as potential targeting ligands because of their chemical synthesis and ease of modification for conjugation. Preclinical studies using aptamer-siRNA chimeras and aptamer targeted nanoparticle therapeutics have been very successful in mouse models of cancer and HIV. In summary aptamers are in several stages of development, from pre-clinical studies to clinical trials and even as FDA approved therapeutics. In this review, we will discuss the current state of aptamers in clinical trials as well as some promising aptamers in pre-clinical development.

Biomateriais para formulações de base nanotecnológica visando terapia gênica ocular

“…17 São estruturas relativamente novas, descobertas no início dos anos 90, obtidas a partir de bibliotecas de oligonucleotídeos por seleção in vitro. 18 Recentemente, foi aprovado o primeiro aptâmero para o tratamento intravítreo de degeneração macular, o pegaptanib (Macugen ® , Pzifer). 19 …”

Osteoprotective Properties of RNA-Containing Drug Osteochondrin S on the Model of Insufficiency of Sex Hormones in Rats

“…RNA-containing drugs can accelerate tissue regeneration upon damage, change the course of the inflammatory process, stimulate subpopulations of lymphocytes, enhance phagocytosis of macrophages and influence the body's responses to tumors and allografts (Afjeh et al, 2013;Dogini et al, 2014;Shu et al, 2014;Zeliadt, 2014). These effects of RNA-containing substances can be useful in correcting of age-associated conditions (Ni et al, 2011;Masuda et al, 2013). The main mass of RNA preparations consists of various variants of micro RNA (mRNA), obtained by RNA interference methods and constituting a promising class of regulatory molecules, however, RNA preparations "native organopreparations" retain a certain value among RNA-containing substances.…”

A specific aptamer-cell penetrating peptides complex delivered siRNA efficiently and suppressed prostate tumor growthin vivo

“…The first aptamer based therapeutic was FDA approved in 2004 for the treatment of age-related macular degeneration and several other aptamers for cancer therapy such as NOX-A12, AS1411 are currently being evaluated in clinical trials. 19,20 Aptamer A10 is known for its high affinity (K D »10 ¡9 M) for Prostate Specific Membrane Antigen (PSMA) 21 and has been used widely in development of PCa therapy. Currently, A10 has been mainly employed to delivery therapeutic siRNA in the form of aptamer-siRNA chimeras and showed to promote regression of PSMA C tumors through intratumor injection.…”