Nanoscale polyelectrolyte complexes encapsulating mRNA and long-chained siRNA for combinatorial cancer gene therapy

Myung Goo Kim; Sung Duk Joa; Ji Hoon Jeong; Sun Hwa Kim

Journal of Industrial and Engineering Chemistry, Vol.64, 430-437, August, 2018

DOI10.1016/j.jiec.2018.04.005 Export Citation

Nanoscale polyelectrolyte complexes encapsulating mRNA and long-chained siRNA for combinatorial cancer gene therapy

Myung Goo Kim^{1, 2}, Sung Duk Joa¹, Ji Hoon Jeong^{2, †}, and Sun Hwa Kim^{1, †}

¹Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 5, Hwarang-ro 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea
²School of Pharmacy, Sungkyunkwan University, 2066, Seobu-ro, Jangan-gu, Suwon 16410, Republic of Korea

E-mail:,

To precisely regulate target genes that are abnormally expressed in cancers, we suggest an RNA-mediated multigene targeting system that co-encapsulates siRNA against vascular endothelial growth factor (VEGF) and mRNA encoding phosphatase and tensin homolog (PTEN). Polymerized long chain siRNAs (LsiRNAs) formed stable and condensed nanocomplexes with mRNAs using thiolated glycol chitosans (tGCs) as gene carriers. The mRNA/L-siRNA/tGC nanocomplexes (MSNs) exhibited efficient intracellular delivery and superior anti-tumor efficiency with simultaneous up and down-regulation of PTEN and VEGF, respectively. The MSN system can be considered as a new platform for cancer gene therapy requiring accurate control of multiple gene expressions.

Keywords:Gene therapy;siRNA;mRNA;Polyelectrolyte complex

[References]

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[Referenced By]

[1] Yin H, Kanasty RL, Eltoukhy AA, Vegas AJ, Dorkin JR, Anderson DG, Nat. Rev. Genet., 15, 541 (2014)

[2] Naldini L, Nature, 526(7573), 351 (2015)

[3] Wittrup A, Lieberman J, Nat. Rev. Genet., 16, 543 (2015)

[4] Sahin U, Kariko K, Tureci O, Nat. Rev. Drug. Discov., 13, 759 (2014)

[5] Katz MG, Fargnoli AS, Williams RD, Bridges CR, Hum. Gene Ther., 24, 914 (2013)

[6] Whitehead KA, Langer R, Anderson DG, Nat. Rev. Drug Discov., 9, 412 (2010)

[7] Kanasty R, Dorkin JR, Vegas A, Anderson D, Nat. Mater., 12(11), 967 (2013)

[8] Park TG, Jeong JH, Kim SW, Adv. Drug Deliv. Rev., 58, 467 (2006)

[9] Ku SH, Jo SD, Lee YK, Kim K, Kim SH, Adv. Drug Deliver. Rev., 104, 16 (2016)

[10] Lee SY, Huh MS, Lee S, Lee SJ, Chung H, Park JH, Oh YK, Choi K, Kim K, Kwon IC, J. Control. Release, 141, 339 (2010)

[11] Lee SJ, Yook S, Yhee JY, Yoon HY, Kim MG, Ku SH, Kim SH, Park JH, Jeong JH, Kwon IC, Lee S, Lee H, Kim K, J. Control. Release, 220, 631 (2015)

[12] Mokhtari RB, Homayouni TS, Baluch N, Morgatskaya E, Kumar S, Das B, Yeger H, Oncotarget, 8, 38022 (2017)

[13] Al-Lazikani B, Banerji U, Workman P, Nat. Biotechnol., 30, 679 (2012)

[14] Lee SJ, Huh MS, Lee SY, Min S, Lee S, Koo H, Chu JU, Lee KE, Jeon H, Choi Y, Choi K, Byun Y, Jeong SY, Park K, Kim K, Kwon IC, Angew. Chem.-Int. Edit., 51, 7203 (2012)

[15] Song MS, Salmena L, Pandolfi PP, Nat. Rev. Mol. Cell Biol., 13, 283 (2012)

[16] Bevilacqua PC, Ritchey LE, Su Z, Assmann SM, Annu. Rev. Genet., 50, 235 (2016)

[17] Kebbekus P, Draper DE, Hagerman P, Biochemistry, 34, 4354 (1995)

[18] Chen H, Meisburger SP, Pabit SA, Sutton JL, Webb WW, Pollack L, Proc. Natl Acad. Sci. U. S. A., 109, 799 (2012)

[19] Meng FH, Hennink WE, Zhong Z, Biomaterials, 30, 2180 (2009)

[20] Nam HY, Kwon SM, Chung H, Lee SY, Kwon SH, Jeon H, Kim Y, Park JH, Kim J, Her S, Oh YK, Kwon IC, Kim K, Jeong SY, J. Control. Release, 135, 259 (2009)

[21] Alimonti A, Carracedo A, Clohessy JG, Trotman LC, Nardella C, et al., Nat. Genet., 42, 454 (2010)

[22] Senger DR, Mol. Biol. Cell., 21, 377 (2010)

[23] Kim MG, Jo SD, Yhee JY, Lee BS, Lee SJ, Park SG, Kang SW, Kim SH, Jeong JH, Biochem. Biophys. Res. Commun., 489(1), 35 (2017)

[24] Lee SJ, Min HS, Ku SH, Son S, Kwon IC, Kim SH, Kim K, Nanomedicine, 9, 1697 (2014)

[25] Na JH, Lee SY, Lee S, Koo H, Min KH, Jeong SY, Yuk SH, Kim K, Kwon IC, J. Control. Release, 163, 2 (2012)

[26] Scholz C, Wagner E, J. Control. Release, 161, 554 (2012)

[27] Guan S, Rosenecker J, Gene Ther., 24, 133 (2017)

[28] Abels JA, Moreno-Herrero F, van der Heijden T, Dekker C, Dekker NH, Biophys. J., 88, 2737 (2005)