2020 年 7 月 2 日更新
略歴
内田智士
工学系研究科バイオエンジニアリング専攻 特任助教 / ナノ医療イノベーションセンター 客員研究員 (兼任)
学歴
2013.03
東京大学大学院医学系研究科内科学専攻博士課程 修了 博士(医学)取得
研究課題「生体適合性高分子ナノミセルを用いたin vivo核酸デリバリー」
2007.03
東京大学医学部医学科 卒業
2000.03
洛南高等学校 卒業
職歴
2016.04 -
東京大学大学院工学系研究科バイオエンジニアリング専攻 特任助教
2013.12 - 2016.03
東京大学大学院医学系研究科附属疾患生命工学センター 特任助教
2013.04 - 2013.11
東京大学大学院医学系研究科附属疾患生命工学センター 特任研究員
2007.04 - 2009.03
北見赤十字病院 初期臨床研修医
受賞歴
2018.06
第10回日本DDS学会奨励賞(臨床)
2016.06
2016年日韓バイオマテリアル学会若手研究者交流AWARD
2014.09
アンチセンス・遺伝子・デリバリーシンポジウム 2014 奨励賞
2014.05
the American Society of Gene and Cell Therapy (ASGCT) 17th Annual Meeting
Outstanding Poster Presentation Award
2012.11
日本バイオマテリアル学会 2012 年優秀ポスター発表賞
2012.07
第 28 回日本 DDS 学会学術集会 優秀発表賞
研究費 (研究代表)
2018 - 2022
科学研究費 基盤研究 (B) 『アジュバント機能一体型mRNAと標的指向性送達キャリアを用いたがんワクチン治療』
2018 - 2021
日本医療研究開発機構 (AMED): 遺伝子・細胞治療研究開発基盤事業 (先端的な遺伝子・細胞治療技術開発) 『RNA工学とペプチド工学の融合による生体内ゲノム編集治療のための技術基盤の開発』
2017 - 2020
科学研究費 挑戦的研究 (萌芽) 『3次元培養幹細胞由来の細胞外小胞体を用いた疾患治療因子の探索』
2017 - 2018
持田記念医学薬学振興財団 研究助成 『疎水基修飾メッセンジャーRNAと標的指向型高分子ミセルを用いた脳梗塞治療』
2016 - 2017
上原記念生命科学財団 研究奨励金
研究課題『神経細胞標的mRNAデリバリーによる脳虚血性疾患治療』
2015 - 2018
武田科学振興財団 医学研究奨励(基礎)
研究課題 『mRNA導入3次元スフェロイド細胞移植による虚血性疾患の治療』
2015 - 2017
科学研究費 若手研究 (B)
研究課題 『mRNA導入による生体内アポトーシスシグナル制御とその虚血性疾患治療への展開』
2014 - 2015
東京医学会研究助成
研究課題 『肝細胞移植における生着率向上を目的とした抗アポトーシス因子発現mRNAの導入』
2013 - 2015
科学研究費 研究活動スタート支援
研究課題 『mRNA 内包ナノミセルを用いた抗アポトーシス因子導入システムの開発とその治療応用』
Selected Papers
  1. T. Miyazaki, S. Uchida, S. Nagatoishi, K. Koji, T. Hong, S. Fukushima, K. Tsumoto, K. Ishihara, K. Kataoka, H. Cabral, Polymeric nanocarriers with controlled chain flexibility boost mRNA delivery in vivo through enhanced structural fastening. Adv. Healthc. Mater. in press
  2. A. Dirisala, S. Uchida, K. Toh, J. Li, S. Osawa, T. A. Tockary, X. Liu, S. Abbasi, K. Hayashi, Y. Mochida, S. Fukushima, H. Kinoh, K. Osada, K. Kataoka, Transient stealth coating of liver sinusoidal wall by anchoring two-armed PEG for retargeting nanomedicines. Sci. Adv. 6 (26) eabb8133 (2020) (DOI: 10.1126/sciadv.abb8133)
  3. S. Uchida, K. Yanagihara, A. Matsui, K. Kataoka, K. Itaka, mRNA as a tool for gene transfection in 3D cell culture for future regenerative therapy. micromachines 11 Issue4 426 (2020) (DOI: 10.3390/mi11040426)
  4. R. Ueki, S. Uchida, N. Kanda, N. Yamada, A. Ueki, M. Akiyama, K. Toh, H. Cabral, S. Sando, A chemically unmodified agonistic DNA with growth factor functionality for in vivo therapeutic application. Sci. Adv. 6 14 eaay2801 (2020) (DOI: 10.1126/sciadv.aay2801)
  5. B. S. Kim, S. Osawa, M. Naito, S. Ogura, R. Kamegawa, H. Ishida, H. J. Kim, S. Uchida, K. Miyata, A 50 nm-sized micellar assembly of thermoresponsive polymer-antisense oligonucleotide conjugates for enhanced gene knockdown in lung cancer by intratracheal administration. Adv. Therap. 3 1900123 (2020) (DOI: 10.1002/adtp.201900123)
  6. T. A. Tockary, W. Foo, A. Dirisala, Q. Chen, S. Uchida, S. Osawa, Y. Mochida, X. Liu, H. Kinoh, H. Cabral, K. Osada, K. Kataoka, Single-stranded DNA-packaged polyplex micelle as adeno-associated-virus-inspired compact vector to systemically target stroma-rich pancreatic cancer. ACS Nano 13 Issue11 12732-12742 (2019) (DOI: 10.1021/acsnano.9b04676)
  7. S. T. Crowley, Y. Fukushima, S. Uchida, K. Kataoka, K. Itaka, Enhancement of motor function 1 recovery after spinal cord injury in mice by delivery of brain derived neurotrophic factor mRNA. Mol. Ther. Nucleic Acids 17 465-476 (2019) (DOI: 10.1016/j.omtn.2019.06.016)
  8. N. Yoshinaga, E. Cho, K. Koji, Y. Mochida, M. Naito, K. Osada, K. Kataoka, H. Cabral, S. Uchida, Bundling mRNA strands to prepare nano-assemblies with enhanced stability towards RNase for in vivo delivery. Angew. Chem. 58 Issue33 11360-11363 (2019) (DOI: 10.1002/anie.201905203)
  9. A. Dirisala, S. Uchida, T. A. Tockary, N. Yoshinaga, J. Li, S. Osawa, L. Gorantla, S. Fukushima, K. Osada, K. Kataoka, Precise tuning of disulphide crosslinking in mRNA polyplex micelles for optimising extracellular and intracellular nuclease tolerability. J. Drug Target. 27 Issue5-6 670-680 (2019) (DOI: 10.1080/1061186X.2018.1550646)
  10. S. Watanabe, K. Hayashi, K. Toh, H. J. Kim, X. Liu, H. Chaya, S. Fukushima, K. Katsushima, Y. Kondo, S. Uchida, S. Ogura, T. Nomoto, H. Takemoto, H. Cabral, H. Kinoh, H. Tanaka, M. R. Kano, Y. Matsumoto, H. Fukuhara, S. Uchida, M. Nangaku, K. Osada, N. Nishiyama, K. Miyata, K. Kataoka, In vivo rendezvous of small nucleic acid drugs with charge-matched block catiomers to target cancer. Nat. Commun. 10 1894 (2019) (DOI: 10.1038/s41467-019-09856-w)
  11. S. Kurimoto, N. Yoshinaga, K. Igarashi, Y. Matsumoto, H. Cabral, S. Uchida, PEG-oligoRNA hybridization of mRNA for developing sterically stable lipid nanoparticles toward in vivo administration. Molecules 24 (7) 1303 (2019) (DOI: 10.3390/molecules24071303)
  12. C. -Y. Lin, S. T. Crowley, S. Uchida, Y. Komaki, K. Kataoka, K. Itaka, Treatment of intervertebral disk disease by administration of messenger RNA encoding a cartilage-anabolic transcription factor. Mol. Ther. Nucleic Acids 16 7 162-171 (2019) (DOI: 10.1016/j.omtn.2019.02.012)
  13. S. Uchida, K. Kataoka, Design concepts of polyplex micelles for in vivo therapeutic delivery of plasmid DNA and messenger RNA. J. Biomed. Mater. Res. A 107 Issue5 978-990 (2019) (DOI: 10.1002/jbm.a.36614)
  14. M. Naito, Y. Otsu, R. Kamegawa, K. Hayashi, S. Uchida, H. -J. Kim, K. Miyata, Tunable non-enzymatic degradability of N-substituted polyaspartamide main chain by amine protonation and alkyl spacer length in side chains for enhanced messenger RNA transfection efficiency. Sci. Technol. Adv. Mater. 20 Issue1 105-115 (2019) (DOI: 10.1080/14686996.2019.1569818)
  15. N. Yoshinaga, S. Uchida, M. Naito, K. Osada, H. Cabral, K. Kataoka, Induced packaging of mRNA into polyplex micelles by regulated hybridization with a small number of cholesteryl RNA oligonucleotides directed enhanced in vivo transfection. Biomaterials 197 255-267 (2019) (DOI: 10.1016/j.biomaterials.2019.01.023)
  16. A. Matsui, S. Uchida, A. Hayashi, K. Kataoka, K. Itaka, Prolonged engraftment of transplanted hepatocytes in the liver by transient pro-survival factor supplementation using ex vivo mRNA transfection. J. Control. Release 285 1-11 (2018) (DOI: 10.1016/j.jconrel.2018.06.033)
  17. K. Yanagihara, S. Uchida, S. Oba, K. Kataoka, K. Itaka, Treatment of bone defects by transplantation of genetically modified mesenchymal stem cell spheroids. Mol. Ther. Methods Clin. Dev. 9 358-366 (2018) (DOI: 10.1016/j.omtm.2018.04.006)
  18. S. Uchida, N. Yoshinaga, K. Yanagihara, E. Yuba, K. Kataoka, K. Itaka, Designing immunostimulatory double stranded messenger RNA with maintained translational activity through hybridization with poly a sequences for effective vaccination. Biomaterials 150 162-170 (2018) (DOI: 10.1016/j.biomaterials.2017.09.033)
  19. N. Yoshinaga, T. Ishii, M. Naito, T. Endo, S. Uchida, H. Cabral, K. Osada, K. Kataoka, Polyplex micelles with phenylboronate/gluconamide crosslinking in the core exerting promoted gene transfection through spatiotemporal responsivity to intracellular pH and ATP concentration. J. Am. Chem. Soc. 139 (51) 18567-18575 (2017) (DOI: 10.1021/jacs.7b08816)
  20. Y. Anraku, H. Kuwahara, Y. Fukusato, A. Mizoguchi, T. Ishii, K. Nitta, Y. Matsumoto, K. Toh, K. Miyata, S. Uchida, K. Nishina, K. Osada, K. Itaka, N. Nishiyama, H. Mizusawa, T. Yamasoba, T. Yokota, K. Kataoka, Glycaemic control boosts glucosylated nanocarrier crossing the BBB into the brain. Nat. Commun. 8 1001 (2017) (DOI: 10.1038/s41467-017-00952-3)
  21. D.-J. Lee, E. Kessel, T. Lehto, X. Liu, N. Yoshinaga, K. Padari, Y.-C. Chen, S. Kempter, S. Uchida, J. O. Rädler, M. Pooga, M.-T. Sheu, K. Kataoka, E. Wagner, Systemic delivery of folate-PEG siRNA lipopolyplexes with enhanced intracellular stability for in vivo gene silencing in leukemia. Bioconjugate Chem. 28 (9) 2393-2409 (2017) (DOI: 10.1021/acs.bioconjchem.7b00383)
  22. F. Perche, S. Uchida, H. Akiba, C.-Y. Lin, M. Ikegami, A. Disrala, T. Nakashima, K. Itaka, K. Tsumoto, K. Kataoka, Improved brain expression of anti-amyloid β scFv by complexation of mRNA including a secretion sequence with PEG-based block catiomer. Curr. Alzheimer Res. 14 (3) 295-302 (2017)
  23. Q. Chen, K. Osada, Z. Ge, S. Uchida, T. A. Tockary, A. Dirisala, A. Matsui, K. Toh, K. M. Takeda, X. Liu, T. Nomoto, T. Ishii, M. Oba, Y. Matsumoto, K. Kataoka, Polyplex micelle installing intracellular self-processing functionalities without free catiomers for safe and efficient systemic gene therapy through tumor vasculature targeting. Biomaterials 113 253-265 (2017) (DOI: 10.1016/j.biomaterials.2016.10.042)
  24. S. Uchida, K. Hayakawa, T. Ogata, S. Tanaka, K. Kataoka, K. Itaka, Treatment of spinal cord injury by an advanced cell transplantation technology using brain-derived neurotrophic factor-transfected mesenchymal stem cell spheroids. Biomaterials 109 1-11 (2016) (DOI: 10.1016/j.biomaterials.2016.09.007)
  25. C.-Y. Lin, F. Perche, M. Ikegami, S. Uchida, K. Kataoka, K. Itaka, Messenger RNA-based therapeutics for brain diseases: An animal study for augmenting clearance of beta-amyloid by intracerebral administration of neprilysin mRNA loaded in polyplex nanomicelles. J. Control. Release 235 268-275 (2016) (DOI: 10.1016/j.jconrel.2016.06.001)
  26. S. Uchida, H. Kinoh, T. Ishii, A. Matsui, T. A. Tockary, K. M. Takeda, H. Uchida, K. Osada, K. Itaka, K. Kataoka, Systemic delivery of messenger RNA for the treatment of pancreatic cancer using polyplex nanomicelles with a cholesterol moiety. Biomaterials 82 221-228 (2016) (DOI: 10.1016/j.biomaterials.2015.12.031)
  27. H. Uchida, K. Itaka, S. Uchida, T. Ishii, T. Suma, K. Miyata, M. Oba, N. Nishiyama, K. Kataoka, Synthetic polyamines to regulate mRNA translation through the preservative binding of eukaryotic initiation factor 4E to the cap structure. J. Am. Chem. Soc. 138 (5) 1478-1481 (2016) (DOI: 10.1021/jacs.5b11726)
  28. H. Aini, K. Itaka, A. Fujisawa, H. Uchida, S. Uchida, S. Fukushima, K. Kataoka, T. Saito, U. -I. Chung, S. Ohba, Messenger RNA delivery of a cartilage-anabolic transcription factor as a disease-modifying strategy for osteoarthritis treatment. Sci. Rep. 6 18743 (2016) (DOI: 10.1038/srep18743)
  29. A. Matsui, S. Uchida, T. Ishii, K. Itaka, K. Kataoka, Messenger RNA-based therapeutics for the treatment of apoptosis-associated diseases. Sci. Rep. 5 15810 (2015) (DOI: 10.1038/srep15810)
  30. Y. Li, K. Osada, Q. Chen, T. A. Tockary, A. Dirisala, K. M. Takeda, S. Uchida, K. Nagata, K. Itaka, K. Kataoka, Toroidal packaging of pDNA into block ionomer micelles exerting promoted in vivo gene expression. Biomacromolecules 16 (9) 2664-2671 (2015) (DOI: 10.1021/acs.biomac.5b00491)
  31. T. Okuda, Y. Suzuki, Y. Kobayashi, T. Ishii, S. Uchida, K. Itaka, K. Kataoka, H. Okamoto, Development of biodegradable polycation-based inhalable dry gene powders by spray freeze drying. Pharmaceutics 7 (3) 233-254 (2015) (DOI: 10.3390/pharmaceutics7030233)
  32. K. Itaka, S. Uchida, A. Matsui, K. Yanagihara, M. Ikegami, T. Endo, T. Ishii, K. Kataoka, Gene transfection toward spheroid cells on micropatterned culture plates for genetically-modified cell transplantation. JoVE 101 e52384 (2015) (DOI: 10.3791/52384)
  33. S. Uchida, K. Kataoka, K. Itaka, Screening of mRNA chemical modification to maximize protein expression with reduced immunogenicity. Pharmaceutics 7 137-151 (2015) (DOI: 10.3390/pharmaceutics7030137)
  34. Q. Chen, K. Osada, M. Pennisi, S. Uchida, T. A. Tockary, A. Dirisala, Y. Li, K. M. Takeda, S. Oniyanagi, K. Itaka, K. Kataoka, A tadpole-shaped gene carrier with distinct phase segregation in a ternary polymeric micelle. Soft Matter 11 (14) 2718-2722 (2015)
  35. K. Hayakawa, S. Uchida, T. Ogata, S. Tanaka, K. Kataoka, K. Itaka, Intrathecal injection of a therapeutic gene-containing polyplex to treat spinal cord injury. J. Control. Release 197 1-9 (2015) (DOI: 10.1016/j.jconrel.2014.10.027)
  36. A. Dirisala, K. Osada, Q. Chen, T. A. Tockary, K. Machitani, S. Osawa, X. Liu, T. Ishii, K. Miyata, M. Oba, S. Uchida, K. Itaka, K. Kataoka, Optimized rod length of polyplex micelles for maximizing transfection efficiency and their performance in systemic gene therapy against stroma-rich pancreatic tumors. Biomaterials 35 (20) 5359-5368 (2014) (DOI: 10.1016/j.biomaterials.2014.03.037)
  37. K. Nagata, K. Itaka, M. Baba, S. Uchida, T. Ishii, K. Kataoka, Muscle-targeted hydrodynamic gene introduction of insulin-like growth factor-1 using polyplex nanomicelle to treat peripheral nerve injury. J. Control. Release 183 27-34 (2014) (DOI: 10.1016/j.jconrel.2014.03.021)
  38. Z. Ge, Q. Chen, K. Osada, X. Liu, T. A. Tockary, S. Uchida, A. Dirisala, T. Ishii, T. Nomoto, K. Toh, Y. Matsumoto, M. Oba, M. R. Kano, K. Itaka, K. Kataoka, Targeted gene delivery by polyplex micelles with crowded PEG palisade and cRGD moiety for systemic treatment of pancreatic tumors. Biomaterials 35 (10) 3416-3426 (2014) (DOI: 10.1016/j.biomaterials.2013.12.086)
  39. S. Uchida, K. Itaka, T. Nomoto, T. Endo, Y. Matsumoto, T. Ishii, K. Kataoka, An injectable spheroid system with genetic modification for cell transplantation therapy. Biomaterials 35 (8) 2499-2506 (2014) (DOI: 10.1016/j.biomaterials.2013.12.012)
  40. T. A. Tockary, K. Osada, Q. Chen, K. Machitani, A. Dirisala, S. Uchida, T. Nomoto, K. Toh, Y. Matsumoto, K. Itaka, K. Nitta, K. Nagayama, K. Kataoka, Tethered PEG crowdedness determining shape and blood circulation profile of polyplex micelle gene carriers. Macromolecules 46 (16) 6585-6592 (2013) (DOI: 10.1021/ma401093z)
  41. H. Takemoto, K. Miyata, S. Hattori, T. Ishii, T. Suma, S. Uchida, N. Nishiyama, K. Kataoka, Acidic pH-responsive siRNA conjugate for reversible carrier stability and accelerated endosomal escape with reduced IFNα-associated immune response. Angew. Chem. Int. Ed. 52 (24) 6218-6221 (2013) (DOI: 10.1002/anie.201300178)
  42. S. Uchida, K. Itaka, H. Uchida, K. Hayakawa, T. Ogata, T. Ishii, S. Fukushima, K. Osada, K. Kataoka, In vivo messenger RNA introduction into the central nervous system using polyplex nanomicelle. PLoS One 8 (2) e56220 (2013) (DOI:10.1371/journal.pone.0056220)
  43. T. Endo, K. Itaka, M. Shioyama, S. Uchida, K. Kataoka, Gene transfection to spheroid culture system on micropatterned culture plate by polyplex nanomicelle: A novel platform of genetically-modified cell transplantation. Drug Deliv. Transl. Res. 2 (5) 398-405 (2012) (DOI: 10.1007/s13346-012-0091-1)
  44. Q. Chen, K. Osada, T. Ishii, M. Oba, S. Uchida, T. A. Tockary, T. Endo, Z. Ge, H. Kinoh, M. R. Kano, K. Itaka, K. Kataoka, Homo-catiomer integration into PEGylated polyplex micelle from block-catiomer for systemic antiangiogenic gene therapy for fibrotic pancreatic tumors. Biomaterials 33 (18) 4722-4730 (2012) (DOI: 10.1016/j.biomaterials.2012.03.017)
  45. S. Uchida, K. Itaka, Q. Chen, K. Osada, T. Ishii, M. A. Shibata, M. Harada-Shiba, K. Kataoka, PEGylated polyplex with optimized PEG shielding enhances gene introduction in lungs by minimizing inflammatory responses. Mol Ther. 20 (6) 1196-1203 (2012) (DOI: 10.1038/mt.2012.20)
  46. T. Suma, K. Miyata, T. Ishii, S. Uchida, H. Uchida, K. Itaka, N. Nishiyama, K. Kataoka, Enhanced stability and gene silencing ability of siRNA-loaded polyion complexes formulated from polyaspartamide derivatives with a repetitive array of amino groups in the side chain. Biomaterials 33 (9) 2770-2779 (2012) (DOI: 10.1016/j.biomaterials.2011.12.022)
  47. S. Uchida, K. Itaka, Q. Chen, K. Osada, K. Miyata, T. Ishii, M. Harada-Shiba, K. Kataoka, Combination of chondroitin sulfate and polyplex micelles from poly(ethylene glycol)-poly{N’-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} block copolymer for prolonged in vivo gene transfection with reduced toxicity. J. Control. Release 155 (2) 296-302 (2011) (DOI: 10.1016/ j.jconrel.2011.04.026)
  48. T. Yoshida, S. Uchida, M. Mishina, Regulation of synaptic vesicle accumulation and axon terminal remodeling during synapse formation by distinct Ca2+ signaling. J. Neurochem. 111 (1) 160-170 (2009)