1. WANG HANLU 2015.9.6 Advance in research of aptamers and related drugs

2. Aptamer Aptamers are oligonucleotides, such as RNA and single-strand deoxyribonucleic acid (ssDNA) or peptide molecules that can bind to their targets with high affinity and specificity due to their specific three-dimensional structures. Advantages of aptamers Aptamers are produced chemically in a readily scalable process Chemical production process is not prone to viral or bacterial contamination Non-immunogenic Smaller size allows more efficient entry into biological compartments

3. The annual trends in the number of publications of aptamers-related research. The term “aptamer” has been utilized for literature search on Thomson Reuters Web of Science. Aptamers in research

4. ELLINGTON AD ， SZOSTAK JW ． In vitro selection of RNA molecules that bind specific ligands ［ J]. Nature ， 1990 ， 346 （ 6287 ）： 818 － 822 ． TUERK C ， GOLD L ． Systematic evolution of ligands by exponential enrichment RNA ligands to bacteriophage-T4 DNA polymerase ［ J] ． Science ， 1990 ， 249 （ 4968 ）： 505 － 510 ． SELEX (Systematic evolution of ligands by exponential enrichment) First reported by both Gold’s group and Szostak’s group in 1990 SELEX experiment: a random sequence oligonucleotide library is synthesized that spans 20–100 residues in length, and each nucleotide is flanked by constant sequences. The pool will frequently contain between 1 × 10 13 to 1 ×10 15 members.

5. Aptamer discovery process

6. Song, K. M. Aptamers and their biological applications. Sensors (Basel).12, 612-31(2012) Various application fields of aptamers

7. Aptamers in the Clinical Pipeline

8. JELLINEK D,GREEN LS,BELL C,et al. Inhibition of receptor-binding by high-affinity RNA ligands to vascular endothelial growth-factor[J]. Biochemistry,1994,33 ( 34 ) : 10450 - 10456. RUCKMAN J,GREEN LS,BEESON J,et al. 2'-fluoropyrimi- dine RNA-based aptamers to the 165-amino acid form of vascular endothelial growth factor ( VEGF ( 165 ) ) -inhibition of receptor binding and VEGF-induced vascular permeability through interac- tions requiring the exon 7-encoded domain[J]. J Biol Chem, 1998,273( 32) : 20556 - 20567. D‘AMICO DJ,MASONSON HN,PATEL M,et al. Pegaptanib sodium for neovascular age- related macular degeneration-Two-year safety results of the two prospective, multicenter, controlled clinical trials[J]. Ophthalmology,2006,113( 6) : 992 - 1001. Pegaptanib——anti-VEGF aptamer

9. Schematic representation of the design of the activatable aptamers probe (AAP) Optical Molecular Imaging with Aptamer-Based Probes Shi H., He X., Wang K., Wu X., Ye X., Guo Q., Tan W., Qing Z., Yang X., Zhou B. Activatable aptamer probe for contrast-enhanced in vivo cancer imaging based on cell membrane protein-triggered conformation alteration. Proc. Natl. Acad. Sci. USA. 2011;108.

10. Optical Molecular Imaging with Aptamer-Based Probes Shi H., He X., Wang K., Wu X., Ye X., Guo Q., Tan W., Qing Z., Yang X., Zhou B. Activatable aptamer probe for contrast-enhanced in vivo cancer imaging based on cell membrane protein-triggered conformation alteration. Proc. Natl. Acad. Sci. USA. 2011;108.

11. Optical Molecular Imaging with Aptamer-Based Probes Shi H., He X., Wang K., Wu X., Ye X., Guo Q., Tan W., Qing Z., Yang X., Zhou B. Activatable aptamer probe for contrast-enhanced in vivo cancer imaging based on cell membrane protein-triggered conformation alteration. Proc. Natl. Acad. Sci. USA. 2011;108.

12. Aptamer-mediated drug delivery Omid C. Farokhzad, Jianjun Cheng, Benjamin A. Teply, et al. Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo. Proc. Natl. Acad. Sci. USA. 2006;103.

13. Aptamer-mediated drug delivery

14. Problems Time-consuming in selection? CE-SELEX, automated screening technology Easy to degrade in vivo? Modified nucleoside, Capping, PEGlyation ， … How to illustrate the binding structure? NMR ， … Not mature for application?