Exclusive: Nanobiomedicine

Molecular element and functionalized nucleic acid

  • TAN Yan ,
  • LI Yingying ,
  • XUAN Wenjing ,
  • WANG Ruowen ,
  • WANG Xueqiang ,
  • TAN Weihong
Expand
  • 1. Molecular Science and Biomedicine Laboratory, College of Chemistry and Chemical Engineering, Hunan University;State Key Laboratory for Chemo/Bio Sensing and Chemometrics, Changsha 410082, China;
    2. Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China

Received date: 2018-07-19

  Revised date: 2018-09-26

  Online published: 2018-12-14

Abstract

We put forward an influential concept of "molecular elements" to appreciate the composition of nucleic acids from a new perspective. The nucleic acids that exhibit different functions are designed based on the functional requirement. They are constructed by phosphodiester bonds formation from various "molecular elements" that have different bases, thus achieving a variety of functions such as specific molecular recognition, catalysis, and intelligent response. In this article we present an overview of representative research results of our laboratory upon functional nucleic acid molecules, including the screening and application of nucleic acid aptamers as macromolecular medicine; the synthesis and evolution of artificial bases; the mechanism of DNAzymes; molecular beacons, molecular motors and their applications in biosensing, biosynthesis, biopharmaceutical research. Moreover, we discuss the challenges and future research directions in the field of functionalized nucleic acid.

Cite this article

TAN Yan , LI Yingying , XUAN Wenjing , WANG Ruowen , WANG Xueqiang , TAN Weihong . Molecular element and functionalized nucleic acid[J]. Science & Technology Review, 2018 , 36(22) : 54 -65 . DOI: 10.3981/j.issn.1000-7857.2018.22.004

References

[1] Zhang Y, Ptacin J L, Fischer E C, et al. A semi-synthetic organism that stores and retrieves increased genetic information[J]. Nature, 2017, 551(7682):644-647.
[2] Jayasena S D. Aptamers:An emerging class of molecules that rival antibodies in diagnostics[J]. Clinical Chemistry, 1999, 45(9):1628-1650.
[3] Keefe A D, Pai S, Ellington A. Aptamers as therapeutics[J]. Nature Reviews:Drug Discovery, 2010, 9(7):537-550.
[4] Shangguan D H, Li Y, Tang Z W, et al. Aptamers evolved from live cells as effective molecular probes for cancer study[J]. PNAS, 2006, 103(32):11838-11843.
[5] Shangguan D H, Meng L, Cao Z C, et al. Identification of liver cancer-specific aptamers using whole live cells[J]. Analytical Chemistry, 2008, 80(3):721-728.
[6] Chen H W, Medley C D, Sefah K, et al. Molecular recognition of small-cell lung cancer cells using aptamers[J]. ChemMedChem:Chemistry Enabling Drug Discovery, 2008, 3(6):991-1001.
[7] Shangguan D H, Cao Z C, Li Y, et al. Aptamers evolved from cultured cancer cells reveal molecular differences of cancer cells in patient samples[J]. Clinical Chemistry, 2007, 53(6):1153-1155.
[8] Tolle F, Brändle M G. Dressed for success-Applying chemistry to modulate aptamer functionality[J]. Chemical Science, 2013, 4(1):60-67.
[9] Zichi D, Eaton B, Singer B, et al. Proteomics and diagnostics:Let's get specific, again[J]. Current Opinion in Chemical Biology, 2008, 12(1):78-85.
[10] Tolle F, Brandle G M, Matzner D, et al. A versatile approach towards nucleobase-modified aptamers[J]. Angewandte Chemie International Edition, 2015, 54(37):10971-10974.
[11] Zhang L Q, Wan S, Jiang Y, et al. Molecular elucidation of disease biomarkers at the interface of chemistry and biology[J]. Journal of the American Chemical Society, 2017, 139(7):2532-2540.
[12] Kimoto M, Yamashige R, Matsunaga K, et al. Generation of high-affinity DNA aptamers using an expanded genetic alphabet[J]. Nature Biotechnology, 2013, 31(5):453-457.
[13] Sefah K, Yang Z, Bradley K M, et al. In vitro selection with artificial expanded genetic information systems[J]. PNAS, 2014, 111(4):1449-1454.
[14] Ren X, Gelinas A D, von Carlowitz I, et al. Structural basis for IL-1alpha recognition by a modified DNA aptamer that specifically inhibits IL-1alpha signaling[J]. Nature Communications, 2017, 8(1):810.
[15] Chen Z, Lichtor P A, Berliner A P, et al. Evolution of sequence-defined highly functionalized nucleic acid polymers[J]. Nature Chemistry, 2018, 10(4):420-427.
[16] Malyshev D A, Seo Y J, Ordoukhanian P, et al. PCR with an expanded genetic alphabet[J]. Journal of the American Chemical Society, 2009, 131(41):14620-14621.
[17] Li L, Degardin M, Lavergne T, et al. Natural-like replication of an unnatural base pair for the expansion of the genetic alphabet and biotechnology applications[J]. Journal of the American Chemical Society, 2014, 136(3):826-829.
[18] Yang Z, Sismour A M, Sheng P, et al. Enzymatic incorporation of a third nucleobase pair[J]. Nucleic Acids Research, 2007, 35(13):4238-4249.
[19] Hirao I, Kimoto M, Mitsui T, et al. An unnatural hydrophobic base pair system:Site-specific incorporation of nucleotide analogs into DNA and RNA[J]. Nature Methods, 2006, 3(9):729-735.
[20] Malyshev D A, Dhami K, Lavergne T, et al. A semi-synthetic organism with an expanded genetic alphabet[J]. Nature, 2014, 509(7500):385-388.
[21] 陈非, 董梦醒, 葛猛, 等. 人造碱基与人工合成生命[J]. 中国科学院院刊, 2016, 31(4):457-466. Chen Fei, Dong Mengxing, Ge Meng, et al. Artificial bases and synthetic life[J]. Bulelletin of Chinese Academy of Sciences, 2016, 31(4):457-466.
[22] Wang R W, Jin C, Zhu X Y, et al. Artificial base zT as functional "element" for constructing photoresponsive DNA nanomolecules[J]. Journal of the American Chemical Society, 2017, 139(27):9104-9107.
[23] Wang R W, Wang C M, Cao Y, et al. Trifluoromethylated nucleic acid analogues capable of self-assembly through hydrophobic interactions[J]. Chemical Science, 2014, 5(10):4076-4081.
[24] Maberley D. Pegaptanib for neovascular age-related macular degeneration[J]. Issues in Emerging Health Technologies, 2005(76):1-4.
[25] Stuart R K, Stockerl-Goldstein K, Cooper M, et al. Randomized phase Ⅱ trial of the nucleolin targeting aptamer AS1411 combined with high-dose cytarabine in relapsed/refractory acute myeloid leukemia (AML)[J]. Journal of Clinical Oncology, 2009, 27(15S):7019-7019.
[26] Dobrovolsky A B, Titaeva E V, Khaspekova S G, et al. Inhibition of thrombin activity with DNA-aptamers[J]. Bulletin of Experimental Biology and Medicine, 2009, 148(1):33-36.
[27] Huang Y F, Shangguan D, Liu H, et al. Molecular assembly of an aptamer-drug conjugate for targeted drug delivery to tumor cells[J]. ChemBioChem, 2009, 10(5):862-868.
[28] Boyacioglu O, Stuart C H, Kulik G, et al. Dimeric DNA aptamer complexes for high-capacity-targeted drug delivery using pH-sensitive covalent linkages[J]. Molecular Therapy-Nucleic Acids, 2013, 2:e107.
[29] Wang R, Zhu G, Mei L, et al. Automated modular synthesis of aptamer-drug conjugates for targeted drug delivery[J]. Journal of the American Chemical Society, 2014, 136(7):2731-2734.
[30] Zhu G Z, Niu G, Chen X Y. Aptamer-drug conjugates[J]. Bioconjugate Chemistry, 2015, 26(11):2186-2197.
[31] Li F F, Lu J, Liu J, et al. A water-soluble nucleolin aptamerpaclitaxel conjugate for tumor-specific targeting in ovarian cancer[J]. Nature Communications, 2017, 8(1):1390.
[32] Gray B P, Kelly L, Ahrens D P, et al. Tunable cytotoxic aptamer-drug conjugates for the treatment of prostate cancer[J]. PNAS, 2018, 115(18):4761-4766.
[33] Zhu G Z, Zheng J, Song E Q, et al. Self-assembled, aptamertethered DNA nanotrains for targeted transport of molecular drugs in cancer theranostics[J]. PNAS, 2013, 110(20):7998-8003.
[34] Zhu G Z, Meng L, Ye M, et al. Self-assembled aptamerbased drug carriers for bispecific cytotoxicity to cancer cells[J]. Chemistry-An Asian Journal, 2012, 7(7):1630-1636.
[35] Chen K, Liu B, Yu B, et al. Advances in the development of aptamer drug conjugates for targeted drug delivery[J]. Wiley Interdisciplinary Reviews:Nanomedicine and Nanobiotechnology, 2017, 9(3):e1438.
[36] Breaker R R, Joyce G F. A DNA enzyme that cleaves RNA[J]. Chemistry and Biology,1994, 1(4):223-229.
[37] Li J, Lu Y. A highly sensitive and selective catalytic DNA biosensor for lead ions[J]. Journal of the American Chemical Society, 2000, 122(42):10466-10467.
[38] Wang H, Kim Y, Liu H P, et al. Engineering a unimolecular DNA-catalytic probe for single lead ion monitoring[J]. Journal of the American Chemical Society, 2009, 131(23):8221-8226.
[39] Kong R M, Zhang X B, Chen Z, et al. Unimolecular catalytic DNA biosensor for amplified detection of L-histidine via an enzymatic recycling cleavage strategy[J]. Analytical Chemistry, 2011, 83(20):7603-7607.
[40] Lu L M, Zhang X B, Kong R M, et al. A ligation-triggered DNAzyme cascade for amplified fluorescence detection of biological small molecules with zero-background signal[J]. Journal of the American Chemical Society, 2011, 133(30):11686-11691.
[41] Zhao X H, Gong L, Zhang X B, et al. Versatile DNAzymebased amplified biosensing platforms for nucleic acid, protein, and enzyme activity detection[J]. Analytical Chemistry, 2013, 85(7):3614-3620.
[42] Fan H H, Zhao Z L, Yan G B, et al. A smart DNAzymeMnO2 nanosystem for efficient gene silencing[J]. Angewandte Chemie International Edition, 2015, 54(16):4801-4805.
[43] Tyagi S, Kramer F R. Molecular beacons:Probes that fluoresce upon hybridization[J]. Nature Biotechnology, 1996, 14(3):303-308.
[44] Goel G, Kumar A, Puniya A K, et al. Molecular beacon:A multitask probe[J]. Journal of Applied Microbiology, 2005, 99(3):435-442.
[45] Tan W, Wang K, Drake T J. Molecular beacons[J]. Current Opinion in Chemical Biology, 2004, 8(5):547-553.
[46] Zheng J, Yang R H, Shi M L, et al. Rationally designed molecular beacons for bioanalytical and biomedical applications[J]. Chemical Society Reviews, 2015, 44(10):3036-3055.
[47] Ellington A D, Szostak J W. In vitro selection of RNA molecules that bind specific ligands[J]. Nature, 1990, 346(6287):818-822.
[48] Zhang X B, Wang Z, Xing H, et al. Catalytic and molecular beacons for amplified detection of metal ions and organic molecules with high sensitivity[J]. Analytical Chemistry, 2010, 82(12):5005-5011.
[49] Thurley S, Roglin L, Seitz O. Hairpin peptide beacon:Duallabeled PNA-peptide-hybrids for protein detection[J]. Journal of the American Chemical Society, 2007, 129(42):12693-12695.
[50] Bratu D P, Cha B J, Mhlanga M M, et al. Visualizing the distribution and transport of mRNAs in living cells[J]. PNAS, 2003, 100(23):13308-13313.
[51] Medley C D, Drake T J, Tomasini J M, et al. Simultaneous monitoring of the expression of multiple genes inside of single breast carcinoma cells[J]. Analytical Chemistry, 2005, 77(15):4713-4718.
[52] Li J J, Tan W. A Single DNA molecule nanomotor[J]. Nano Letters, 2002, 2(4):315-318.
[53] Kang H, Liu H, Phillips J A, et al. Single-DNA molecule nanomotor regulated by photons[J]. Nano Letters, 2009, 9(7):2690-2696.
[54] Peng L, You M X, Yuan Q, et al. Macroscopic volume change of dynamic hydrogels induced by reversible DNA hybridization[J]. Journal of the American Chemical Society, 2012, 134(29):12302-12307.
[55] You M X, Huang F J, Chen Z, et al. Building a nanostructure with reversible motions using photonic energy[J]. ACS Nano, 2012, 6(9):7935-7941.
Outlines

/