eISSN: 2221-6197 DOI: 10.31301/2221-6197

Химический синтез олигонуклеотидов: этапы 70-летнего пути

Год: 2026

Страницы: 178-214

Номер: Том 18, № 2

Тип: научная статья

Аннотация:

Более 70 лет назад, в августе 1955 г., вышла статья, в которой описан первый синтез динуклеотидов с природной фосфодиэфирной связью. За прошедшие годы химический синтез олигонуклеотидов претерпел серьезную эволюцию, пройдя различные этапы: от фосфотриэфирного, через фосфонатный, фосфодиэфирный, фосфиттриэфирный, преобразованный затем в амидофосфитный. Последний является в настоящее время основным методом синтеза олигонуклеотидов с помощью автоматических ДНК-синтезаторов. В целом, амидофосфитный способ обеспечивает решение текущих задач науки и практики, за исключением получения протяженных олигонуклеотидов и крупномасштабного синтеза. Однако потребность в олигонуклеотидах будет неизбежно расти, в том числе их модифицированных форм, как в плане разнообразия, так и в количественном отношении. При этом должны будут интенсивно развиваться как твердофазный колоночный и микрочиповый синтезы, так и синтез в жидкой фазе, способный обеспечить производство килограммовых количеств терапевтических олигонуклеотидов. Можно прогнозировать, что потребность в относительно коротких олигонуклеотидах для сельского хозяйства через некоторое время будет измеряться тоннами.

Ключевые слова:

олигонуклеотид, химический синтез олигонуклеотидов, амидофосфитный метод, ДНК-синтезатор, твердофазный колоночный синтез, микрочиповый синтез, синтез олигонуклеотидов в жидкой фазе

Библиографический список:

    1. Добрынин В.Н., Филиппов С.А., Быстров Н.С. и др. Катализируемый метилимидазолом быстрый синтез олигодезоксинуклеотидовфосфотриэфирным путем на силикагельном носителе в дихлорэтане. Биоорг. химия. 1983. 9(5). 706-710.
    2. Гарафутдинов Р.Р., Никоноров Ю.М., Сахабутдинова А.Р. и др. Ферментативный синтез олигонуклеотидов. Biomics. 2025. 17(4). С.337-351. doi: 10.31301/2221-6197.bmcs.2025-30
    3. Грязнов С.М., Потапов В.К., Горн В.В. и др. Полный автоматический синтез фосфотриэфирным методом олигодезоксинуклеотидов на синтезаторе «Виктория-4М». Биополимеры и клетка. 1986. 2(6). 311–316.
    4. Женодарова С.М., Хабарова М.И. Химические методы синтеза полинуклеотидов. Успехи химии. 1966. 35(7). 1265-1276.
    5. Зарытова В.Ф., Потапов В.К., Шабарова 3.А. и др. Синтез олиглуклеотидов на полимерных носителях. Синтез олигодезоксинуклеотидов, содержащих дезоксигуаниловую кислоту. Доклады Академии наук СССР. 1971. 199(5). 1072 -1074.
    6. Купрюшкин М.С., Пышный Д.В., Стеценко Д.А. Фосфорилгуанидины. Новый класс аналогов нуклеиновых килсот. Acta Naturae. 2014. 6(4). 123-125.
    7. Ломакин А.И., Попов С.Г. Автоматический синтез олигодезоксирибонуклеотидов. II. Использование сегментных носителей на основе целлюлозы. Биоорган. химия. 1985. 11(7). 927-933.
    8. Ломакин А.И., Ястребов С.И., Попов С.Г. Автоматический синтез олигодезоксирибонуклеотидов. I. Исследование носителей на основе силикагеля марки «Силохром». Биоорган. химия. 11(7). 920-926.
    9. Оберемок В.В., Лайкова Е.В., Зайцев А.С. и др. Создание ДНК-инсектицидов – новое направление в защите растений. Защита и карантин растений. 2026. (11). 14-16.
    10. Потапов В.К., Звездина В.В., Кочеткова М.Н. и др. Препаративный синтез олигонуклеотидных блоков на высокосшитом полимерном носителе. Доклады Академии наук СССР. 1973. 209(2). 364–366.
    11. Потапов В.К., Потемкин В.К., Горн В.В. и др. Полуавтоматический твердофазный синтез олигодезоксирибонуклеотидов. Доклады Академии наук СССР. 263(6). 1386–1389.
    12. Потапов В.К., Туркин С.И., Вейко В.П. и др. Использование нового типа полимерного носителя в синтезе олигонуклеотидов. Доклады Академии наук СССР. Химия. 1978. 241(6). 1352 – 1354.
    13. Потапов В.К., Чехмачева О.Г., Шабарова 3.А. и др. Синтез олигонуклеотидов на полимерных носителях. Синтез дезокси-[тимидили-(3`→5`)-аденилил-(3`→5`) аденилил-(3`→5`)-аденозина. Доклады Академии наук СССР. 196(2). 360–363.
    14. Сахабутдинова А.Р., Михайленко К.И., Гарафутдинов Р.Р. и др. «Водяные ДНК-знаки» в виде встроенных в геномы различных организмов чужеродных последовательностей ДНК и не только встроенных. Biomics. 13(4). 368-386. DOI: 10.31301/2221-6197.bmcs.2021-26
    15. Синяков А.Н., Костина Е.В. Методы очистки синтетических олигонуклеотидов и исправления ошибок в синтетической ДНК. Молекулярная Биология. 2025. 59(4). 544–556. doi: 10.31857/S0026898425040021
    16. Чемерис А.В., Аминев Ф.Г., Гарафутдинов Р.Р. и др. ДНК-криминалистика. М.: Наука. 2022. 466 С.
    17. Abramova T. Frontiers and approaches to chemical synthesis of oligodeoxyribonucleotides. Molecules. 2013. 18(1). 1063-75. doi: 10.3390/molecules18011063
    18. Adams SP, Kavka KS, Wykes EJ et al. Hindered dialkylamino nucleoside phosphite reagents in the synthesis of two DNA 51-mers. Am. Chem. Soc. 1983. 105(3). 661-663. doi: 10.1021/ja00341a078
    19. Agarwal KL, Büchi H, Caruthers MH et al. Total synthesis of the gene for an alanine transfer ribonucleic acid from yeast. Nature. 1970. 227(5253). 27-34. doi: 10.1038/227027a0
    20. Albert TJ, Norton J, Ott M et al. Light-directed 5`-->3` synthesis of complex oligonucleotide microarrays. Nucleic Acids Res. 2003. 31(7). e35. doi: 10.1093/nar/gng035
    21. Alekseev YI, Krynetskaya NF, Tashlytsky VN et al. Interaction of Escherichia coli ribonuclease H with hybrid duplexes containing 2'-deoxyxylothymidine, 2'-deoxy-2' fluorouridine or alpha-thymidine. Nucleosides and Nucleotides. 1996. 15(9). 1545-1558. doi: 10.1080/07328319608002453
    22. Alvarado-Urbina G, Sathe GM, Liu WC et al. Automated synthesis of gene fragments. Science. 1981. 214(4518). 270-274. doi: 10.1126/science.6169150
    23. Amarnath V, Broom AD. Chemical synthesis of oligonucleotides. Chemical Reviews. 1977. 77(2). 183–217. doi:10.1021/cr60306a002
    24. Anderson NG, Anderson NL, Taylor J et al. Large-scale oligonucleotide synthesizers. Basic principles and system design. Appl Biochem Biotechnol. 1995. 54(1-3). 19-42. doi: 10.1007/BF02787909
    25. Andrews BI, Antia FD, Brueggemeier SB et al. Sustainability Challenges and Opportunities in Oligonucleotide Manufacturing. Org. Chem. 2021. 86(1). 49-61. doi: 10.1021/acs.joc.0c02291
    26. Beaucage SL, Caruthers MH. Deoxynucleoside phosphoramidites - A new class of key intermediates for deoxypolynucleotide synthesis. Tetrahedron Letters. 1981. 22(20). 1859-1862. doi: 10.1016/S0040-4039(01)90461-7
    27. Beaucage SL, Iyer RP. Advances in the Synthesis of Oligonucleotides by the Phosphoramidite Approach. Tetrahedron. 1982. 48(12). 2223-2311. doi: 10.1016/S0040-4020(01)88752-4
    28. Beier M, Hoheisel JD. Analysis of DNA-microarrays produced by inverse in situ oligonucleotide synthesis. J Biotechnol. 94(1). 15-22. doi: 10.1016/s0168-1656(01)00416-3
    29. Belikova AM, Zarytova VF, Grineva NI. Synthesis of ribonucleosides and diribonucleoside phosphates containing 2-chloroethylamine and nitrogen mustard residues. Tetrahedron Lett. 1967. 37. 3557-3562. doi: 10.1016/s0040-4039(01)89794-x.
    30. Benner SA. Magnetic particles as supports for organic synthesis. US Patent No 4,638,032. Jan. 20, 1987.
    31. Blair S, Richmond K, Rodesch M et al. A scalable method for multiplex LED-controlled synthesis of DNA in capillaries. Nucleic Acids Res. 2006. 34(16). e110. doi: 10.1093/nar/gkl641
    32. Blanchard AP, Kaiser RJ, Hood LE. High-density oligonucleotide arrays. Biosensors and Bioelectronics. 1996. 11(6–7). 687-690. doi: 10.1016/0956-5663(96)83302-1
    33. Bonora GM, Biancotto G, Maffini M et al. Large scale, liquid phase synthesis of oligonucleotides by the phosphoramidite approach. Nucleic Acids Res. 1993. 21(5). 1213-1217. doi: 10.1093/nar/21.5.1213
    34. Bonora GM, Rossin R, Zaramella S et al. A Liquid-Phase Process Suitable for Large-Scale Synthesis of Phosphorothioate Oligonucleotides. Process Res. Dev. 2000. 4(3). 225 – 231. doi: 10.1021/op990096l
    35. Bonora GM, Scremin CL, Colonna FP et al. HELP (high efficiency liquid phase) new oligonucleotide synthesis on soluble polymeric support. Nucleic Acids Res. 18(11). 3155-3159. doi: 10.1093/nar/18.11.3155
    36. Brown D.M. A brief history of oligonucleotide synthesis. Methods Mol Biol. 1993. 20. 1-17. doi: 10.1385/0-89603-281-7:1
    37. Brzezinska J, Trzciński S, Strzelec J et al. From CPG to hybrid support: Review on the approaches in nucleic acids synthesis in various media. Bioorg Chem. 2023. 140. 106806. doi: 10.1016/j.bioorg.2023.106806
    38. Caruthers MH. Gene synthesis machines: DNA chemistry and its uses. Science. 1985. 230(4723). 281-285. doi: 10.1126/science.3863253
    39. Caruthers Chemical synthesis of DNA and DNA analogs. Acc. Chem. Res. 1991. 24(9). 278-284. doi: 10.1021/ar00009a005
    40. Caruthers MH. The chemical synthesis of DNA/RNA: our gift to science. J Biol Chem. 2013. 288(2). 1420-1427. doi: 10.1074/jbc.X112.442855
    41. Caruthers MH, Beaucage SL, Becker C et al. Deoxyoligonucleotide synthesis via the phosphoramidite method. Gene Amplif Anal. 1983. 3. 1-26.
    42. Catlin JC, Cramer F. Deoxy oligonucleotide synthesis via the triester method. Org. Chem. 1973. 38(2). 245–250. doi: 10.1021/jo00942a011
    43. Cheng JY, Chen HH, Kao YS et al. High throughput parallel synthesis of oligonucleotides with 1536 channel synthesizer. Nucleic Acids Res. 2002. 30(18). e93. doi: 10.1093/nar/gnf092
    44. Cook AF, Holman MJ, Nussbaum AL. Nucleoside S-alkyl phosphorothioates. III. Application to oligonucleotide synthesis. Am. Chem. Soc. 1969. 91(23). 6479–6484. doi: 10.1021/ja01051a052
    45. Cramer F, Helbig R, Hettler H et al. Oligonucleotide Synthesis with a Soluble Polymer as Carrier. Chem. Int. Edit. 1966. 5(6). 601.
    46. Crea R, Horn T. Synthesis of oligonucleotides on cellulose by a phosphotriester method. Nucleic Acids Res. 1980. 8(10). 2331-2348. doi: 10.1093/nar/8.10.2331
    47. Crea R, Kraszewski A, Hirose T et al. Chemical synthesis of genes for human insulin. Proc Natl Acad Sci USA. 1978. 75(12). 5765-5769. doi: 10.1073/pnas.75.12.5765
    48. deHaseth PL, Goldman RA, Cech CL et al. Chemical synthesis and biochemical reactivity of bacteriophage lambda PR promoter. Nucleic Acids Res. 1983. 11(3). 773-787. doi: 10.1093/nar/11.3.773
    49. Delavari A, Keykhasaber M, Miri MA et al. Control of Phytophthora capsici, which causes root and stem rot, using encapsulated oligonucleotide DNA. Sci Rep. 2026. 16(1). 4215. doi: 10.1038/s41598-025-34330-7
    50. Dellinger DJ, Betley JR, Wyrzykiewicz TK et al. Synthesis of DNA using a new two-step cycle. Methods Mol Biol. 2005. 288. 1-16. doi: 10.1385/1-59259-823-4:001
    51. Donga RA, Hassler M, Chan TH et al. Oligonucleotide synthesis using ionic liquids as soluble supports. Nucleosides Nucleotides Nucleic Acids. 2007. 26(10-12). 1287-1293. doi: 10.1080/15257770701530533
    52. Donga RA, Khaliq-Uz-Zaman SM, Chan TH et al. A novel approach to oligonucleotide synthesis using an imidazolium ion tag as a soluble support. J Org Chem. 2006. 71(20). 7907-7910. doi: 10.1021/jo061279q
    53. Eckstein F, Rizk I. Synthesis of oligonucleotides by use of phosphoric triesters. Chem. Int. Ed. Engl. 1967. 6(8). 695-697. doi: 10.1002/anie.196706951
    54. Edge MD, Green AR, Heathcliffe GR et al. Total synthesis of a human leukocyte interferon gene. Nature. 1981. 292(5825). 756-762. doi: 10.1038/292756a0
    55. Efimov VA, Buryakova AA, Dubey IY et al. Application of new catalytic phosphate protecting groups for the highly efficient phosphotriester oligonucleotide synthesis. Nucleic Acids Res. 14(16). 6525-6540. doi: 10.1093/nar/14.16.6525
    56. Efimov VA, Reverdatto SV, Chakhmakhcheva OG. New effective method for the synthesis of oligonucleotides via phosphotriester intermediates. Nucleic Acids Res. 1982. 10(21). 6675-6694. doi: 10.1093/nar/10.21.6675
    57. Egeland RD, Marken F, Southern EM. An Electrochemical Redox Couple Activitated by Microelectrodes for Confined Chemical Patterning of Surfaces. Analytical Chemistry. 74(7). 1590-1596. doi: 10.1021/ac010953v
    58. Egeland RD, Southern EM. Electrochemically directed synthesis of oligonucleotides for DNA microarray fabrication. Nucleic Acids Res. 2005. 33(14). e125. doi: 10.1093/nar/gni117
    59. Fang S, Arneson R, Yin Y et al. De Novo Synthesis of Error-Free Long Oligos. Curr Protoc. 2024. 4(10). e70028. doi: 10.1002/cpz1.70028
    60. Fang S, Fueangfung S. Scalable synthetic oligodeoxynucleotide purification with use of a catching by polymerization, washing, and releasing approach. Org Lett. 2010. 12(16). 3720-3723. doi: 10.1021/ol101316g
    61. Fiers W, Khorana HG. Studies on polynucleotides. XXII. Enzymic degradation. An exonuclease from lactobacillus acidophilus R26. A. Purification, properties, and substrate specificity. J Biol Chem. 1963. 238(8). 2780-2788. doi: 10.1016/S0021-9258(18)67897-4
    62. Fodor SP, Read JL, Pirrung MC et al. Light-directed, spatially addressable parallel chemical synthesis. Science. 1991. 251(4995). 767-773. doi: 10.1126/science.1990438
    63. Frank R, Heikens W, Heisterberg-Moutsis G et al. A new general approach for the simultaneous chemical synthesis of large numbers of oligonucleotides: segmental solid supports. Nucleic Acids Res. 1983. 11(13). 4365-4377. doi: 10.1093/nar/11.13.4365
    64. Froehler BC, Ng PG, Matteucci MD. Synthesis of DNA via deoxynucleoside H-phosphonate intermediates. Nucleic Acids Res. 1986. 14(13). 5399–5407. doi: 10.1093/nar/14.13.5399
    65. Gaffney PRJ, Jarrett-Wilkins C, Yeo J et al. Fully Liquid Phase Oligonucleotide Synthesis. Organic Process Research & Development. 2026. 30(1). 98-120. doi: 10.1021/acs.oprd.5c00346
    66. Gaffney PR, Kim JF, Valtcheva IB et al. Liquid-Phase Synthesis of 2`-Methyl-RNA on a Homostar Support through Organic-Solvent Nanofiltration. Chemistry. 2015. 21(26). 9535-9543. doi: 10.1002/chem.201501001
    67. Gait MJ, Matthes HW, Singh M et al. Rapid synthesis of oligodeoxyribonucleotides. VII. Solid phase synthesis of oligodeoxyribonucleotides by a continuous flow phosphotriester method on a kieselguhr-polyamide support. Nucleic Acids Res. 1982. 10(20). 6243-6254. doi: 10.1093/nar/10.20.6243
    68. Gait MJ, Sheppard RC. Rapid synthesis of oligodeoxyribonucleotides: a new solid-phase method. Nucleic Acids Res. 1977. 4(4). 1135-1158. doi: 10.1093/nar/4.4.1135
    69. Gait MJ, Sheppard RC. Rapid synthesis of oligodeoxyribonucleotides. II. Machine-aided solid-phase syntheses of two nonanucleotides and an octanucleotide. Nucleic Acids Res. 1977. 4(12). 4391-4410. doi: 10.1093/nar/4.12.4391
    70. Gait MJ, Singh M, Sheppard RC et al. Rapid synthesis of oligodeoxyribonucleotides. IV. Improved solid phase synthesis of oligodeoxyribonucleotides through phosphotriester intermediates. Nucleic Acids Res. 1980. 8(5). 1081-10 doi: 10.1093/nar/8.5.1081
    71. Gao X, Gulari E, Zhou X. In situ synthesis of oligonucleotide microarrays. Biopolymers. 2004. 73(5). 579-596. doi: 10.1002/bip.20005
    72. Garafutdinov RR, Chemeris DA, Sakhabutdinova AR et al. Encoding of non-biological information for its long-term storage in DNA. Biosystems. 2022. 215-216. 104664. doi: 10.1016/j.biosystems.2022.104664
    73. Garegg PJ, Lindh I, Regberg T et al. Nucleoside H-phosphonates. III. Chemical synthesis of oligodeoxyribonucleotides by the hydrogenphosphonate approach. Tetrahedron Letters. 1986. 27. 4051-4054. doi: 10.1016/S0040-4039(00)84908-4
    74. Giannaris PA, Damha MJ. Hybridization properties of oligoarabinonucleotides. J. Chem. 1994. 72(3). 909-918. doi: 10.1139/v94-118
    75. Gibson DG, Benders GA, Andrews-Pfannkoch C et al. Complete chemical synthesis, assembly, and cloning of a Mycoplasma genitalium Science. 2008. 319(5867). 1215-20. doi: 10.1126/science.1151721
    76. Gibson DG, Glass JI, Lartigue C, et al. Creation of a bacterial cell controlled by a chemically synthesized genome. Science. 2010. 329(5987). 52-56. doi: 10.1126/science.1190719
    77. Gilham PT, Khorana HG. Studies on polynucleotides. I. A new and general method for the chemical synthesis of the C5″-C3″ Internucleotidic linkage. syntheses of deoxyribo-dinucleotides1. Am. Chem. Soc. 1958. 80(23). 6212–6222. doi: 10.1021/ja01556a016
    78. Goeddel DV, Yansura DG, Caruthers MH. Studies on gene control regions. 1. Chemical synthesis of lactose operator deoxyribonucleic acid segments. Biochemistry. 1977. 16(9). 1765-1772. doi: 10.1021/bi00628a001
    79. Gravert DJ, Janda KD. Organic Synthesis on Soluble Polymer Supports:  Liquid-Phase Methodologies. Rev. 1997. 97(2). 489–510. doi: 10.1021/cr960064l
    80. Hall RH, Todd A, Webb RF. Nucleotides. Part XLI. Mixed anhydrides as intermediates in the synthesis of dinucleoside phosphates. Chem. Soc. 1957. 3291-3296. doi: 10.1039/JR9570003291
    81. Hamada S, Murayama K, Takezawa Y et al. Omega Nucleic Acids (ΩNA), Ultimate Nucleic Acids for Future Technology. Molecules. 2026. 31(3). 523. doi: 10.3390/molecules31030523
    82. Hayatsu H, Khorana HG. Deoxyribooligonucleotide Synthesis on a Polymeric Support. Am. Chem. Soc. 1966. 88(13). 3182–3183. doi: 10.1021/ja00965a086
    83. Hayatsu H, Khorana HG. Studies on polynucleotides. LXXII. Deoxyribooligonucleotide synthesis on a polymer support. J Am Chem Soc. 1967. 89(15). 3880-3887. doi: 10.1021/ja00991a035
    84. Heinonen P, Lönnberg H. Synthesis of phosphate-branched oligonucleotides. Bioconjug Chem. 2004 Nov-Dec;15(6):1158-60. doi: 10.1021/bc049845g
    85. Hirose T, Crea R, Itakura K. Rapid synthesis of trideoxyribonucleotide blocks. Tetrahedron Letters. 1978. 19(28). 2449-2452. doi: 10.1016/S0040-4039(01)94797-5
    86. Hogrefe RI, Midthune B, Lebedev A. Current Challenges in Nucleic Acid Synthesis. Isr. J. Chem. 2013. 53(6-7). 326-349. doi: 10.1002/ijch.201300032
    87. Hölz K, Hoi JK, Schaudy E et al. High-Efficiency Reverse (5`→3`) Synthesis of Complex DNA Microarrays. Sci Rep. 8(1). 15099. doi: 10.1038/s41598-018-33311-3
    88. Horn T, Chang CA, Urdea MS. Chemical synthesis and characterization of branched oligodeoxyribonucleotides (bDNA) for use as signal amplifiers in nucleic acid quantification assays. Nucleic Acids Res. 1997. 25(23). 4842-4849. doi: 10.1093/nar/25.23.4842
    89. Huang Y, Knouse KW, Qiu S et al. A P(V) platform for oligonucleotide synthesis. Science. 2021. 373(6560). 1265-1270. doi: 10.1126/science.abi9727
    90. Hunkapiller M, Kent S, Caruthers M et al. A microchemical facility for the analysis and synthesis of genes and proteins. Nature. 1984. 310(5973). 105-111. doi: 10.1038/310105a0
    91. Huo C, Chan TH. A novel liquid-phase strategy for organic synthesis using organic ions as soluble supports. Chem Soc Rev. 39(8). 2977-3006. doi: 10.1039/b914497h
    92. Inagawa T, Nakashima H, Karwowski B et al. Inhibition of human immunodeficiency virus type 1 replication by P-stereodefined oligo(nucleoside phosphorothioate)s in a long-term infection model. FEBS Lett. 2002. 528(1-3). 48-52. doi: 10.1016/s0014-5793(02)03235-0
    93. Itakura K, Bahl CP, Katagiri N et al. A Modified Triester Method for the Synthesis of Deoxyribopolynucleotides. J. Chem. 1973. 51. 3649–3651.doi:10.1139/v73-543
    94. Itakura K, Katagiri N, Narang SA et al. Chemical synthesis and sequence studies of deoxyribooligonucleotides which constitute the duplex sequence of the lactose operator of Escherichia coli. J Biol Chem. 1975. 250(12). 4592-4600. doi: 10.1016/S0021-9258(19)41343-4
    95. Jensen M, Roberts L, Johnson A et al. Next generation 1536-well oligonucleotide synthesizer with on-the-fly dispense. Biotechnol. 2014. 171. 76-81. doi: 10.1016/j.jbiotec.2013.11.027
    96. Jensen MA, Akhras MS, Fukushima M et al. Direct oligonucleotide synthesis onto super-paramagnetic beads. J Biotechnol. 2013. 167(4). 448-453. doi: 10.1016/j.jbiotec.2013.08.006
    97. Jensen TB, Langkjaer N, Wengel J. Unlocked nucleic acid (UNA) and UNA derivatives: thermal denaturation studies. Nucleic Acids Symp Ser (Oxf). (52). 133-134. doi: 10.1093/nass/nrn068
    98. Jo S, Shin H, Joe SY et al. Recent progress in DNA data storage based on high-throughput DNA synthesis. Biomed Eng Lett. 14(5). 993-1009. doi: 10.1007/s13534-024-00386-z
    99. Kamaike K, Hasegawa Y, Ishido Y. Efficient syntheses of an oligonucleotide on a cellulose acetate derivative as a novel polymer-support using phosphotriester approach. Tetrahedron Letters. 1988. 29(6). 647–650. doi: 10.1016/S0040-4039(00)80172-0
    100. Kaplan BE. The automated synthesis of oligodeoxyribonucleotides. Trends in Biotechnology. 1985. 3(10). 253-256. doi: 10.1016/0167-7799(85)90024-1
    101. Kashida H, Murayama K, Toda T et al. Control of the chirality and helicity of oligomers of serinol nucleic acid (SNA) by sequence design. Angew Chem Int Ed Engl. 2011. 50(6). 1285-1288. doi: 10.1002/anie.201006498
    102. Katayama S, Hirai K. Liquid-Phase Synthesis of Oligonucleotides. In: Obika S, Sekine M. (eds) Synthesis of Therapeutic Oligonucleotides. Springer, Singapore. 83-95. doi: 10.1007/978-981-13-1912-9_5
    103. Kayushin AL, Korosteleva MD, Miroshnikov AI et al. A convenient approach to the synthesis of trinucleotide phosphoramidites--synthons for the generation of oligonucleotide/peptide libraries. Nucleic Acids Res. 1996. 24(19). 3748-3755. doi: 10.1093/nar/24.19.3748
    104. Khorana HG. Nucleic acid synthesis. Pure Appl. Chem. 17. 349-381. doi: 10.1351/pac196817030349
    105. Khorana HG. Total synthesis of a gene. Science. 1979. 203(4381). 614-625. doi: 10.1126/science.366749
    106. Khorana HG, Razzell WE, Gilham PT et al. Syntheses of dideoxyribonucleotides. Am. Chem. Soc. 1957. 79(4). 1002-1003. doi: 10.1021/ja01561a065
    107. Khorana HG. Todd AR. Studies on phosphorylation. Part XI. The reaction between carbodi-imides and acid esters of phosphoric acid. A new method for the preparation of pyrophosphates. Journal of the Chemical Society. 1953. 2257-2260. doi: 10.1039/jr9530002257
    108. Kim J, Kim H, Bang D. OpenIDS2: A low-cost, 3D-printed, open-source platform for reproducible construction of DNA microarray synthesizers. PLoS One. 2025. 20(12). e0338478. doi: 10.1371/journal.pone.0338478
    109. Kim J, Kim H, Bang D. An open-source, 3D printed inkjet DNA synthesizer. Sci Rep. 2024. 14(1). 3773. doi: 10.1038/s41598-024-53944-x
    110. Knouse KW, deGruyter JN, Schmidt MA et al. Unlocking P(V): Reagents for chiral phosphorothioate synthesis. Science. 2018. 361(6408). 1234-1238. doi: 10.1126/science.aau3369
    111. Kogan SC, Doherty M, Gitschier J. An improved method for prenatal diagnosis of genetic diseases by analysis of amplified DNA sequences. Application to hemophilia A. New Engl J Med. 1987. 317(16). 985-990. doi: 10.1056/NEJM198710153171603
    112. Köster H. Polymer support oligonucleotide synthesis VI use of inorganic carriers. Tetrahedron Letters. 1972. 13(16). 1527-1530. doi: 10.1016/S0040-4039(01)84677-3
    113. Köster H. Polymer support oligonucleotide synthesis VIII use of polyethylenglycol. Tetrahedron Letters. 1972a. 13(16). 1534-1538. doi: 1016/S0040-4039(01)84679-7
    114. Köster H, Stumpe A, Wolter A. Polymer support oligonucleotide synthesis 13: Rapid and efficient synthesis of oligodeoxynucleotides on porous glass support using triester approach. Tetrahedron Letters. 1983. 24(8). 747-750. doi: 10.1016/S0040-4039(00)81515-4
    115. Koziołkiewicz M, Wójcik M, Kobylańska A et al. Stability of stereoregular oligo(nucleoside phosphorothioate)s in human plasma: diastereoselectivity of plasma 3'-exonuclease. Antisense Nucleic Acid Drug Dev. 1997. 7(1). 43-48. doi: 10.1089/oli.1.1997.7.43
    116. Kozlov IA, Dang M, Sikes K et al. Significant improvement of quality for long oligonucleotides by using controlled pore glass with large pores. Nucleosides Nucleotides Nucleic Acids. 24(5-7). 1037-1041. doi: 10.1081/ncn-200059761
    117. Krasnodębski C, Sawuła A, Kaźmierczak U et al. Oligo-Not Only for Silencing: Overlooked Potential for Multidirectional Action in Plants. Int J Mol Sci. 2023. 24(5). 4466. doi: 10.3390/ijms24054466
    118. Kraszewski A, Stawiński J. H-Phosphonates: Versatile synthetic precursors to biologically active phosphorus compounds. Pure and Applied Chemistry. 2007. 79(12). 2217 – 2227. doi:10.1351/pac200779122217
    119. Kumar V, Gore KR, Pradeepkumar PI et al. Design, synthesis, biophysical and primer extension studies of novel acyclic butyl nucleic acid (BuNA). Org Biomol Chem. 2013. 11(35). 5853-5865. doi: 10.1039/c3ob41244j
    120. Kungurtsev V, Laakkonen J, Molina AG et al. Solution-Phase Synthesis of Short Oligo-2′-deoxyribonucleotides by Using Clustered Nucleosides as a Soluble Support. Eur. J. Org. Chem. 2013. 6687-6693. doi: 10.1002/ejoc.201300864
    121. Lashkari DA, Hunicke-Smith SP, Norgren RM et al. An automated multiplex oligonucleotide synthesizer: development of high-throughput, low-cost DNA synthesis. Proc Natl Acad Sci USA. 1995. 92(17). 7912-7915. doi: 10.1073/pnas.92.17.7912
    122. LeProust EM, Peck BJ, Spirin K et al. Synthesis of high-quality libraries of long (150mer) oligonucleotides by a novel depurination controlled process. Nucleic Acids Res. 2010. 38(8). 2522-2540. doi: 10.1093/nar/gkq163
    123. Letsinger RL, Caruthers MH, Miller PS et al. Oligonucleotide syntheses utilizing beta-benzoylpropionyl, a blocking group with a trigger for selective cleavage. J Am Chem Soc. 1967. 89(26). 7146-7147. doi: 10.1021/ja01002a074
    124. Letsinger RI, Finnan JL, Heavner GA et al. Letter: Phosphite coupling procedure for generating internucleotide links. J Am Chem Soc. 1975. 97(11). 3278-3279. doi: 10.1021/ja00844a090
    125. Letsinger RL, Lunsford WB. Synthesis of thymidine oligonucleotides by phosphite triester intermediates. J Am Chem Soc. 1976. 98(12). 3655-3661. doi: 10.1021/ja00428a045
    126. Letsinger RL, Mahadevan V. Oligonucleotide Synthesis on a Polymer Support. Am. Chem. Soc. 1965. 87(15). 3526–3527. doi: 10.1021/ja01093a058
    127. Letsinger RL, Mahadevan V. Stepwise synthesis of oligodeoxyribonucleotides on an insoluble polymer support. J Am Chem Soc. 1966. 88(22). 5319-5324. doi: 10.1021/ja00974a053
    128. Letsinger RL, Ogilvie KK. Nucleotide chemistry. XIII. Synthesis of oligothymidylates via phosphotriester intermediates. Am. Chem. Soc. 1969. 91(12). 3350–3355. doi: 0.1021/ja01040a042
    129. Li H, Huang Y, Wei Z et al. An oligonucleotide synthesizer based on a microreactor chip and an inkjet printer. Sci Rep. 2019. 9(1). 5058. doi: 10.1038/s41598-019-41519-0
    130. Liu ZC, Shin DS, Shokouhimehr M et al. Light-directed synthesis of peptide nucleic acids (PNAs) chips. Biosens Bioelectron. 2007. 22(12). 2891-2897. doi: 10.1016/j.bios.2006.12.005
    131. Lohrmann R, Söll D, Hayatsu H et al. Studies on polynucleotides. LI. Syntheses of the 64 possible ribotrinucleotides derived from the four major ribomononucle J Am Chem Soc. 1966. 88(4). 819-829. doi: 10.1021/ja00956a039
    132. Lönnberg H. Synthesis of oligonucleotides on a soluble support. Beilstein J Org Chem. 2017. 13. 1368-1387. doi: 10.3762/bjoc.13.134
    133. Lu Y. Recent advances in the stereocontrolled synthesis of antisense phosphorothioates. Mini Rev Med Chem. 2006. 6(3). 319-330. doi: 10.2174/138955706776073439
    134. Ma Y, Zhang Z, Jia B et al. Automated high-throughput DNA synthesis and assembly. Heliyon. 2024. 10(6). e doi: 10.1016/j.heliyon.2024.e26967
    135. Marshall WS, Caruthers MH. Phosphorodithioate DNA as a potential therapeutic drug. Science. 1993. 259(5101). 1564-1570. doi: 10.1126/science.7681216
    136. Matteucci MD, Caruthers MH. The synthesis of oligodeoxyprimidines on a polymer support. Tetrahedron Letters. 1980. 21(8). 719-722. doi: 10.1016/S0040-4039(00)71455-9
    137. Matteucci MD, Caruthers MH. Synthesis of deoxyoligonucleotides on a polymer support. Am. Chem. Soc. 1981. 103(11). 3185-3191. doi: 10.1021/ja00401a041
    138. Matthes HW, Zenke WM, Grundström T et al. Simultaneous rapid chemical synthesis of over one hundred oligonucleotides on a microscale. EMBO J. 3(4). 801-805. doi: 10.1002/j.1460-2075.1984.tb01888.x
    139. McBride L.J., Caruthers M.H. An investigation of several deoxynucleoside phosphoramidites useful for synthesizing deoxyoligonucleotides. Tetrahedron Letters. 24. 245-248. doi: 10.1016/S0040-4039(00)81376-3
    140. McGall G, Labadie J, Brock P et al. Light-directed synthesis of high-density oligonucleotide arrays using semiconductor photoresists. Proc Natl Acad Sci USA. 1996. 93(24). 13555-13560. doi: 10.1073/pnas.93.24.13555
    141. Michelson AM. Polynucleotides. Part IV. Synthesis of oligonucleotide analogous substituted in the sugar portion. Journal of the Chemical Society. 1962. 979–982. doi: 10.1039/JR9620000979
    142. Michelson AM, Todd AR. Nucleotides part XXXII. Synthesis of a dithymidine dinucleotide containing a 3′:5′-internucleotidic linkage. Chem. Soc. 1955. 2632-2638. doi: 10.1039/JR9550002632
    143. Miyazaki Y, Yoshida A, Okaniwa T et al. Oligonucleotide Synthesis on Porous Glass Resins Containing Activators. Org Lett. 2022. 24(21). 3807-3811. doi: 10.1021/acs.orglett.2c01348
    144. Mohammed AA, AlShaer D, Al Musaimi O. Oligonucleotides: evolution and innovation. Medicinal Chemistry Research. 2024. 33. 2204–2220. doi:: 10.1007/s00044-024-03352-7
    145. Molina AG, Kungurtsev V, Virta P et al. Acetylated and methylated β-cyclodextrins as viable soluble supports for the synthesis of short 2′-oligodeoxyribo-nucleotides in solution. Molecules. 2012. 17(10). 12102-20. doi: 10.3390/molecules171012102
    146. Molina AG, Sanghvi YS. Liquid-Phase Oligonucleotide Synthesis: Past, Present, and Future Predictions. Curr Protoc Nucleic Acid Chem. 2019. 77(1). doi: 10.1002/cpnc.82
    147. Narang CK, Brunfeldt K, Norris KE. Oligonucleotide synthesis on a crosslinked polyacrylmorpholide support. Tetrahedron Letters. 1977. 18(21). 1819-1822. doi: 10.1016/S0040-4039(01)83614-5
    148. Narang SA, Brousseau R, Hsiung HM et al. Chemical synthesis of deoxyoligonucleotides by the modified triester method. Methods Enzymol. 1980. 65(1). 610-620. doi: 10.1016/s0076-6879(80)65063-0
    149. Narang SA, Hsiung HM, Brousseau R. Improved phosphotriester method for the synthesis of gene fragments. Methods Enzymol. 1979. 68. 90-98. doi: 10.1016/0076-6879(79)68008-4
    150. Nassir M, Gherardi L, Redman RL et al. An Improved P(V) Thio-Oligonucleotide Synthesis Platform. Org Lett. 2025. 27(1). 97-102. doi: 10.1021/acs.orglett.4c03980
    151. Nguyen BH, Takahashi CN, Gupta G et al. Scaling DNA data storage with nanoscale electrode wells. Sci Adv. 2021. 7(48). eabi6714. doi: 10.1126/sciadv.abi6714
    152. Nielsen P, Dreiøe LH, Wengel J. Synthesis and evaluation of oligodeoxynucleotides containing acyclic nucleosides: introduction of three novel analogues and a summary. Bioorg Med Chem. 1995. 3(1). 19-28. doi: 10.1016/0968-0896(94)00143-q
    153. Nielsen PE, Egholm M, Berg RH et al. Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide. Science. 1991. 254(5037). 1497-500. doi: 10.1126/science.1962210
    154. Oberemok VV, Useinov RZ, Skorokhod OA et al. Oligonucleotide Insecticides for Green Agriculture: Regulatory Role of Contact DNA in Plant-Insect Interactions. Int J Mol Sci. 23(24). 15681. doi: 10.3390/ijms232415681
    155. Obika S, Morio K, Nanbu D et al. Synthesis and conformation of 3′-O,4′-C-methyleneribonucleosides, novel bicyclic nucleoside analogues for 2′,5′-linked oligonucleotide modification. Commun. 1997. (17). 1643–1644. doi: 10.1039/A704376G
    156. O`Callaghan DM, Donnelly WJ. Oligonucleotide synthesis using the manual phosphotriester method. Methods Mol Biol. 1988. 4. 165-192. doi: 10.1385/0-89603-127-6:165
    157. Ono A, Matsuda A, Zhao J et al. The synthesis of blocked triplet-phosphoramidites and their use in mutagenesis. Nucleic Acids Res. 23(22). 4677-4682. doi: 10.1093/nar/23.22.4677
    158. Organick L, Ang SD, Chen YJ et al. Random access in large-scale DNA data storage. Biotechnol. 2018. 36(3). 242-248. doi: 10.1038/nbt.4079
    159. Ott J, Eckstein F. Filter disc supported oligonucleotide synthesis by the phosphite method. Nucleic Acids Res. 1984. 12(23). 9137-9142. doi: 10.1093/nar/12.23.9137
    160. Pease AC, Solas D, Sullivan EJ et al. Light-generated oligonucleotide arrays for rapid DNA sequence analysis. Proc Natl Acad Sci USA. 1994. 91(11). 5022-5026. doi: 10.1073/pnas.91.11.5022
    161. Pon RT. Solid-phase supports for oligonucleotide synthesis. Methods Mol Biol. 1993. 20. 465-496. doi: 10.1385/0-89603-281-7:465
    162. Pon RT. Chemical Synthesis of Oligonucleotides: From Dream to Automation. In book: Artificial DNA. Methods and Applications. Eds Khudyakov YuE, Fields HA. 2002. CRC Press. 1-80.
    163. Potapov VK, Veiko VP, Koroleva ON et al. Rapid synthesis of oligodeoxyribonucleotides on a grafted polymer support. Nucleic Acids Res. 1979. 6(6). 2041-2056. doi: 10.1093/nar/6.6.2041
    164. Rebimbas R, Glória I, Chegão J et al. DNA as a data storage medium. J Biotechnol. 414. 19-35. doi: 10.1016/j.jbiotec.2026.03.003
    165. Reese CB. Oligo- and poly-nucleotides: 50 years of chemical synthesis. Org Biomol Chem. 2005. 3(21). 3851-3868. doi: 10.1039/B510458K
    166. Reese CB, Saffhill R. Oligonucleotide synthesis via phosphotriester intermediates: the phenyl-protecting group. Chemical Comm. (London). (13). 767-768. doi: 10.1039/C1968000076
    167. Rosenqvist P, Saari V, Pajuniemi E et al. Stereo-Controlled Liquid Phase Synthesis of Phosphorothioate Oligonucleotides on a Soluble Support. Org. Chem. 2023. 88(14). 10156–10163. doi: 10.1021/acs.joc.3c01006
    168. Sabatino D, Damha MJ. Oxepane nucleic acids: synthesis, characterization, and properties of oligonucleotides bearing a seven-membered carbohydrate ring. J Am Chem Soc. 2007. 129(26). 8259-8270. doi: 10.1021/ja071336c
    169. Saiki RK, Gelfand DH, Stoffel S et al. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988. 239(4839). 487-491. doi: 10.1126/science.2448875
    170. Saiki RK, Scharf S, Faloona F et al. Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science. 1985. 230(4732). 1350-1354. doi: 10.1126/science.2999980
    171. Schaller H, Weimann G, Lerch B et al. Studies on Polynucleotides. XXIV. The Stepwise Synthesis of Specific Deoxyribopolynucleotides (4). Protected Derivatives of Deoxyribonucleosides and New Syntheses of Deoxyribonucleoside-3″ Phosphates. Am. Chem. Soc. 1963. 85(23). 3821–3827. doi: 10.1021/ja00906a021
    172. Schöning K, Scholz P, Guntha S et al. Chemical etiology of nucleic acid structure: the alpha-threofuranosyl-(3'→2') oligonucleotide system. Science. 290(5495). 1347-1351. doi: 10.1126/science.290.5495.1347
    173. Schott H. Polyvinyl Alcohol Substituted by Nucleotides as Carrier for Liquid Phase Oligonucleotide Synthesis. Chem. Int. Ed. Engl. 1973. 12. 246-246. doi: 10.1002/anie.197302461
    174. Shemyakin MM, Ovchinnikov YuA, Kinyushkin AA et al. Synthesis of peptides in solution on a polymeric support I. Synthesis of glycylglycyl-l-leucylglycine. Tetrahedron Letters. 1965. 6(27). 2323-2327. doi: 10.1016/S0040-4039(00)70379-0
    175. Shchepinov MS, Mir KU, Elder JK et al. Oligonucleotide dendrimers: stable nano-structures. Nucleic Acids Res. 1999. 27(15). 3035-3041. doi: 10.1093/nar/27.15.3035
    176. Shchepinov MS, Udalova IA, Bridgman AJ et al. Oligonucleotide dendrimers: synthesis and use as polylabelled DNA probes. Nucleic Acids Res. 25(22). 4447-4454. doi: 10.1093/nar/25.22.4447
    177. Shi A, Liu L, Wang F et al. A practical dinucleotide phosphoramidite chemistry for de novo DNA synthesis via block coupling. Tetrahedron Letters. 2024. 142. 155106. doi: 10.1016/j.tetlet.2024.155106
    178. Sierzchala AB, Dellinger DJ, Betley JR et al. Solid-phase oligodeoxynucleotide synthesis: a two-step cycle using peroxy anion deprotection. J Am Chem Soc. 2003. 125(44). 13427-13441. doi: 10.1021/ja030376n
    179. Singh A, Tolev M, Schilling CI et al. Solution-Phase Synthesis of Branched DNA Hybrids via H-Phosphonate Dimers. Org. Chem. 2012. 77(6). 2718–2728. doi: 10.1021/jo202508n
    180. Singh SK, Koshkin AA, Wengel J et al. LNA (locked nucleic acids): synthesis and high-affinity nucleic acid recognition. Commun. 1998. (4). 455 - 456. doi: 10.1039/a708608c
    181. Singh-Gasson S, Green RD, Yue Y et al. Maskless fabrication of light-directed oligonucleotide microarrays using a digital micromirror array. Nat Biotechnol. 1999. 17(10). 974-978. doi: 10.1038/13664
    182. Sinha ND, Biernat J, McManus J et al. Polymer support oligonucleotide synthesis XVIII: use of beta-cyanoethyl-N,N-dialkylamino-/N-morpholino phosphoramidite of deoxynucleosides for the synthesis of DNA fragments simplifying deprotection and isolation of the final product. Nucleic Acids Res. 1984. 12(11). 4539-4557. doi: 10.1093/nar/12.11.4539
    183. Sondek J, Shortle D. A general strategy for random insertion and substitution mutagenesis: substoichiometric coupling of trinucleotide phosphoramidites. Proc Natl Acad Sci USA. 1992. 89(8). 3581-3585. doi: 10.1073/pnas.89.8.3581
    184. Stec WJ, Zon G, Egan W. Automated solid-phase synthesis, separation, and stereochemistry of phosphorothioate analogs of oligodeoxyribonucleotides. Am. Chem. Soc. 1984. 106. 6077 – 6079. doi: 10.1021/ja00332a054
    185. Steffens R, Leumann CJ. Synthesis and thermodynamic and biophysical properties ofTricyclo-DNA. Am. Chem. Soc. 1999. 121(14). 3249 – 3255.doi: 10.1021/ja983570w
    186. Stirchak EP, Summerton JE, Weller DD. Uncharged stereoregular nucleic acid analogs: 2. Morpholino nucleoside oligomers with carbamate internucleoside linkages. Nucleic Acids Res. 1989 Aug 11;17(15):6129-41. doi: 10.1093/nar/17.15.6129
    187. Talap J, Zhao J, Shen M et al. Recent advances in therapeutic nucleic acids and their analytical methods. Pharm. Biomed. Anal. 2021. 206. 114368. doi: 10.1016/j.jpba.2021.114368.
    188. Tanaka T., Letsinger R.L. Syringe method for stepwise chemical synthesis of oligonucleotides. Nucleic Acids Research. 1982. V. 10(10). P. 3249–3260. doi: 10.1093/nar/10.10.3249
    189. Tanaka S, Yukami S, Fukushima K et al. Bulk pH-Responsive DNA Quadruplex Hydrogels Prepared by Liquid-Phase, Large-Scale DNA Synthesis. ACS Macro Lett. 7(3). 295-299. doi: 10.1021/acsmacrolett.8b00063
    190. Tedebark U, Scozzari A, Werbitzky O et al. Industrial-scale manufacturing of a possible oligonucleotide cargo CPP-based drug. Methods Mol Biol. 2011. 683. 505-524. doi: 10.1007/978-1-60761-919-2_36
    191. Templeton NS. The polymerase chain reaction. History, methods, and applications. Diagn Mol Pathol. 1992. 1(1). 58-72. doi: 10.1097/00019606-199203000-00008
    192. Tian J, Gong H, Sheng N et al. Accurate multiplex gene synthesis from programmable DNA microchips. Nature. 2004. 432(7020). 1050-1054. doi: 10.1038/nature03151
    193. Trzciński S, Brzezinska J, Waligórski K et al. Hybrid Supports for Oligonucleotide Synthesis: Controlled Pore Glass Derivatives with Branched Amine-Ended Polyether or Polyimine. Chemistry. 2024. 30(69). e202403086. doi: 10.1002/chem.202403086
    194. Urata H, Ogura E, Shinohara K et al. Synthesis and properties of mirror-image DNA. Nucleic Acids Res. 1992. 20(13). 3325-3332. doi: 10.1093/nar/20.13.3325
    195. Van Aerschot A, Verheggen I, Hendrix C et al. 1,5-Anhydrohexitol nucleic acids, a new promising antisense construct. Chem. Int. Ed. Engl. 1995. 34. 1338-1339. doi: 10.1002/anie.199513381
    196. Virnekäs B, Ge L, Plückthun A et al. Trinucleotide phosphoramidites: ideal reagents for the synthesis of mixed oligonucleotides for random mutagenesis. Nucleic Acids Res. 1994. 22(25). 5600-5607. doi: 10.1093/nar/22.25.5600
    197. Virta P. From liquid-phase synthesis to chemical ligation: preparation of oligonucleotides and their backbone analogs in solution. Nucleic Acids Res. 2025. 53(20). gkaf1084. doi: 10.1093/nar/gkaf1084
    198. Wagner T, Pfleiderer W. Synthesis of 2`-deoxyribonucleoside 5`-phosphoramidites: New building blocks for the inverse (5`-3`)-oligonucleotide approach. Helvetica Chimica Acta. 2000. 83(8). 2023-2035. doi: 10.1002/1522-2675(20000809)83:8<2023::AID-HLCA2023>3.0.CO;2-P
    199. Wang J, Verbeure B, Luyten I et al. Cyclohexene Nucleic Acids (CeNA):  Serum Stable Oligonucleotides that Activate RNase H and Increase Duplex Stability with Complementary RNA. Am. Chem. Soc. 2000.122(36). 8595–8602. doi: 10.1021/ja000018+
    200. Warner BD, Warner ME, Karns GA et al. Construction and evaluation of an instrument for the automated synthesis of oligodeoxyribonucleotides. DNA. 1984. 3(5). 401-411. doi: 10.1089/dna.1984.3.401
    201. Weimann G, Khorana HG. Studies on Polynucleotides. XIII.1 Stepwise Synthesis of Deoxyribo-oligonucleotides. An Alternative General Approach and the Synthesis of Thymidine Di-, Tri- and Tetranucleotides Bearing 3″-Phosphomonoester End Groups2. Am. Chem. Soc. 1962. 84(3). 419–430. doi: 10.1021/ja00862a022
    202. White H.A. Manual oligonucleotide synthesis using the phosphoramidite method. New Nucleic Acid Techniques 4. 193-213. doi: 10.1385/0-89603-127-6:193
    203. Willems PJ. Primer availability. Nature. 1989. 337. 10. DOI: 10.1038/337010b0
    204. Yakovleva KI, Pereverzev IM, Kechin AA et al. The Influence of the Capping Step During Solid-Phase Phosphoramidite Synthesis of Oligonucleotides on Synthetic Errors in Oligonucleotides. Molecules. 2025. 31(1). 94. doi: 10.3390/molecules31010094
    205. Yin Y, Arneson R, Apostle A et al. Long oligodeoxynucleotides: chemical synthesis, isolation via catching-by-polymerization, verification via sequencing, and gene expression demonstration. Beilstein J Org Chem. 2023. 19. 1957-1965. doi: 10.3762/bjoc.19.146
    206. Yin Y, Arneson R, Yuan Y et al. Long oligos: direct chemical synthesis of genes with up to 1728 nucleotides. Chem Sci. 2024. 16(4). 1966-1973. doi: 10.1039/d4sc06958g
    207. Yu M, Tang X, Li Z et al. High-throughput DNA synthesis for data storage. Chem Soc Rev. 2024. 53(9). 4463-4489. doi: 10.1039/d3cs00469d
    208. Zaramella S, Bonora GM. The Application of H-Phosphonate Chemistry in the HELP Synthesis of Oligonucleotides. Nucleosides and Nucleotides. 1995. 14(3–5). 809–812. doi: 10.1080/15257779508012477
    209. Zhang L, Peritz A, Meggers E. A simple glycol nucleic acid. J Am Chem Soc. 2005. 127(12). 4174-4175. doi: 10.1021/ja042564z
    210. Zhdanov RI, Zhenodarova SM. Chemical Methods of Oligonucleotide Synthesis. Synthesis. 1975. 4. 222-245. doi: 10.1055/s-1975-23714
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