Molecularly engineered siRNA conjugates for tumor-targeted RNAi therapy
RNA interference (RNAi) is a major cellular mechanism regulating gene expression in which short double-stranded RNA molecules called small interfering RNA (siRNA) mediate sequence-specific mRNA degradation. RNAi technology has recently emerged as a promising therapeutic platform for the effective tr...
Ausführliche Beschreibung
Autor*in: |
Lee, Jong Won [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
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2022transfer abstract |
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Umfang: |
14 |
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Übergeordnetes Werk: |
Enthalten in: 537 Early, intermediate and late recurrence after radical cystectomy due to bladder cancer: The necessity of a tailored follow up - Moschini, M. ELSEVIER, 2015, official journal of the Controlled Release Society and of the Japanese Society of Drug Delivery Systems, New York, NY [u.a.] |
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Übergeordnetes Werk: |
volume:351 ; year:2022 ; pages:713-726 ; extent:14 |
Links: |
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DOI / URN: |
10.1016/j.jconrel.2022.09.040 |
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520 | |a RNA interference (RNAi) is a major cellular mechanism regulating gene expression in which short double-stranded RNA molecules called small interfering RNA (siRNA) mediate sequence-specific mRNA degradation. RNAi technology has recently emerged as a promising therapeutic platform for the effective treatment of various diseases caused by inappropriate gene activity, such as cancer. However, the clinical translation of siRNA therapeutics has been hampered by the major hurdles associated with biological instability and limited delivery efficiency. Based on the various efforts, recent siRNA delivery strategies using cationic lipids and polymers allowed to enhance pharmacokinetics and delivery efficiency, resulting in potent and liver-targeted RNAi therapy. However, non-specific protein adsorption, high liver accumulation, and severe toxicity of cationic nanocarriers still limit the possibility of transfer of siRNA therapeutics from the laboratory to the clinic. One of the promising delivery strategies to overcome the limitations of siRNA therapeutics is carrier-free bioconjugation which is chemically modified and connected with biocompatible molecules such as lipids, peptides, antibodies, aptamers, and polymers. These molecularly engineered siRNA conjugates can be utilized for RNAi delivery to tissues beyond the liver, providing opportunities for clinical translation. This review focused on introducing the recent progress in molecularly engineered siRNA conjugates and their applications toward overcoming the limitations of siRNA for tumor-targeted delivery and therapy. | ||
520 | |a RNA interference (RNAi) is a major cellular mechanism regulating gene expression in which short double-stranded RNA molecules called small interfering RNA (siRNA) mediate sequence-specific mRNA degradation. RNAi technology has recently emerged as a promising therapeutic platform for the effective treatment of various diseases caused by inappropriate gene activity, such as cancer. However, the clinical translation of siRNA therapeutics has been hampered by the major hurdles associated with biological instability and limited delivery efficiency. Based on the various efforts, recent siRNA delivery strategies using cationic lipids and polymers allowed to enhance pharmacokinetics and delivery efficiency, resulting in potent and liver-targeted RNAi therapy. However, non-specific protein adsorption, high liver accumulation, and severe toxicity of cationic nanocarriers still limit the possibility of transfer of siRNA therapeutics from the laboratory to the clinic. One of the promising delivery strategies to overcome the limitations of siRNA therapeutics is carrier-free bioconjugation which is chemically modified and connected with biocompatible molecules such as lipids, peptides, antibodies, aptamers, and polymers. These molecularly engineered siRNA conjugates can be utilized for RNAi delivery to tissues beyond the liver, providing opportunities for clinical translation. This review focused on introducing the recent progress in molecularly engineered siRNA conjugates and their applications toward overcoming the limitations of siRNA for tumor-targeted delivery and therapy. | ||
700 | 1 | |a Choi, Jiwon |4 oth | |
700 | 1 | |a Choi, Yeonho |4 oth | |
700 | 1 | |a Kim, Kwangmeyung |4 oth | |
700 | 1 | |a Yang, Yoosoo |4 oth | |
700 | 1 | |a Kim, Sun Hwa |4 oth | |
700 | 1 | |a Yoon, Hong Yeol |4 oth | |
700 | 1 | |a Kwon, Ick Chan |4 oth | |
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10.1016/j.jconrel.2022.09.040 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001959.pica (DE-627)ELV059447508 (ELSEVIER)S0168-3659(22)00635-6 DE-627 ger DE-627 rakwb eng 610 VZ 670 VZ 35.80 bkl Lee, Jong Won verfasserin aut Molecularly engineered siRNA conjugates for tumor-targeted RNAi therapy 2022transfer abstract 14 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier RNA interference (RNAi) is a major cellular mechanism regulating gene expression in which short double-stranded RNA molecules called small interfering RNA (siRNA) mediate sequence-specific mRNA degradation. RNAi technology has recently emerged as a promising therapeutic platform for the effective treatment of various diseases caused by inappropriate gene activity, such as cancer. However, the clinical translation of siRNA therapeutics has been hampered by the major hurdles associated with biological instability and limited delivery efficiency. Based on the various efforts, recent siRNA delivery strategies using cationic lipids and polymers allowed to enhance pharmacokinetics and delivery efficiency, resulting in potent and liver-targeted RNAi therapy. However, non-specific protein adsorption, high liver accumulation, and severe toxicity of cationic nanocarriers still limit the possibility of transfer of siRNA therapeutics from the laboratory to the clinic. One of the promising delivery strategies to overcome the limitations of siRNA therapeutics is carrier-free bioconjugation which is chemically modified and connected with biocompatible molecules such as lipids, peptides, antibodies, aptamers, and polymers. These molecularly engineered siRNA conjugates can be utilized for RNAi delivery to tissues beyond the liver, providing opportunities for clinical translation. This review focused on introducing the recent progress in molecularly engineered siRNA conjugates and their applications toward overcoming the limitations of siRNA for tumor-targeted delivery and therapy. RNA interference (RNAi) is a major cellular mechanism regulating gene expression in which short double-stranded RNA molecules called small interfering RNA (siRNA) mediate sequence-specific mRNA degradation. RNAi technology has recently emerged as a promising therapeutic platform for the effective treatment of various diseases caused by inappropriate gene activity, such as cancer. However, the clinical translation of siRNA therapeutics has been hampered by the major hurdles associated with biological instability and limited delivery efficiency. Based on the various efforts, recent siRNA delivery strategies using cationic lipids and polymers allowed to enhance pharmacokinetics and delivery efficiency, resulting in potent and liver-targeted RNAi therapy. However, non-specific protein adsorption, high liver accumulation, and severe toxicity of cationic nanocarriers still limit the possibility of transfer of siRNA therapeutics from the laboratory to the clinic. One of the promising delivery strategies to overcome the limitations of siRNA therapeutics is carrier-free bioconjugation which is chemically modified and connected with biocompatible molecules such as lipids, peptides, antibodies, aptamers, and polymers. These molecularly engineered siRNA conjugates can be utilized for RNAi delivery to tissues beyond the liver, providing opportunities for clinical translation. This review focused on introducing the recent progress in molecularly engineered siRNA conjugates and their applications toward overcoming the limitations of siRNA for tumor-targeted delivery and therapy. Choi, Jiwon oth Choi, Yeonho oth Kim, Kwangmeyung oth Yang, Yoosoo oth Kim, Sun Hwa oth Yoon, Hong Yeol oth Kwon, Ick Chan oth Enthalten in Elsevier Moschini, M. ELSEVIER 537 Early, intermediate and late recurrence after radical cystectomy due to bladder cancer: The necessity of a tailored follow up 2015 official journal of the Controlled Release Society and of the Japanese Society of Drug Delivery Systems New York, NY [u.a.] (DE-627)ELV012920894 volume:351 year:2022 pages:713-726 extent:14 https://doi.org/10.1016/j.jconrel.2022.09.040 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_22 GBV_ILN_40 GBV_ILN_105 35.80 Makromolekulare Chemie VZ AR 351 2022 713-726 14 |
spelling |
10.1016/j.jconrel.2022.09.040 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001959.pica (DE-627)ELV059447508 (ELSEVIER)S0168-3659(22)00635-6 DE-627 ger DE-627 rakwb eng 610 VZ 670 VZ 35.80 bkl Lee, Jong Won verfasserin aut Molecularly engineered siRNA conjugates for tumor-targeted RNAi therapy 2022transfer abstract 14 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier RNA interference (RNAi) is a major cellular mechanism regulating gene expression in which short double-stranded RNA molecules called small interfering RNA (siRNA) mediate sequence-specific mRNA degradation. RNAi technology has recently emerged as a promising therapeutic platform for the effective treatment of various diseases caused by inappropriate gene activity, such as cancer. However, the clinical translation of siRNA therapeutics has been hampered by the major hurdles associated with biological instability and limited delivery efficiency. Based on the various efforts, recent siRNA delivery strategies using cationic lipids and polymers allowed to enhance pharmacokinetics and delivery efficiency, resulting in potent and liver-targeted RNAi therapy. However, non-specific protein adsorption, high liver accumulation, and severe toxicity of cationic nanocarriers still limit the possibility of transfer of siRNA therapeutics from the laboratory to the clinic. One of the promising delivery strategies to overcome the limitations of siRNA therapeutics is carrier-free bioconjugation which is chemically modified and connected with biocompatible molecules such as lipids, peptides, antibodies, aptamers, and polymers. These molecularly engineered siRNA conjugates can be utilized for RNAi delivery to tissues beyond the liver, providing opportunities for clinical translation. This review focused on introducing the recent progress in molecularly engineered siRNA conjugates and their applications toward overcoming the limitations of siRNA for tumor-targeted delivery and therapy. RNA interference (RNAi) is a major cellular mechanism regulating gene expression in which short double-stranded RNA molecules called small interfering RNA (siRNA) mediate sequence-specific mRNA degradation. RNAi technology has recently emerged as a promising therapeutic platform for the effective treatment of various diseases caused by inappropriate gene activity, such as cancer. However, the clinical translation of siRNA therapeutics has been hampered by the major hurdles associated with biological instability and limited delivery efficiency. Based on the various efforts, recent siRNA delivery strategies using cationic lipids and polymers allowed to enhance pharmacokinetics and delivery efficiency, resulting in potent and liver-targeted RNAi therapy. However, non-specific protein adsorption, high liver accumulation, and severe toxicity of cationic nanocarriers still limit the possibility of transfer of siRNA therapeutics from the laboratory to the clinic. One of the promising delivery strategies to overcome the limitations of siRNA therapeutics is carrier-free bioconjugation which is chemically modified and connected with biocompatible molecules such as lipids, peptides, antibodies, aptamers, and polymers. These molecularly engineered siRNA conjugates can be utilized for RNAi delivery to tissues beyond the liver, providing opportunities for clinical translation. This review focused on introducing the recent progress in molecularly engineered siRNA conjugates and their applications toward overcoming the limitations of siRNA for tumor-targeted delivery and therapy. Choi, Jiwon oth Choi, Yeonho oth Kim, Kwangmeyung oth Yang, Yoosoo oth Kim, Sun Hwa oth Yoon, Hong Yeol oth Kwon, Ick Chan oth Enthalten in Elsevier Moschini, M. ELSEVIER 537 Early, intermediate and late recurrence after radical cystectomy due to bladder cancer: The necessity of a tailored follow up 2015 official journal of the Controlled Release Society and of the Japanese Society of Drug Delivery Systems New York, NY [u.a.] (DE-627)ELV012920894 volume:351 year:2022 pages:713-726 extent:14 https://doi.org/10.1016/j.jconrel.2022.09.040 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_22 GBV_ILN_40 GBV_ILN_105 35.80 Makromolekulare Chemie VZ AR 351 2022 713-726 14 |
allfields_unstemmed |
10.1016/j.jconrel.2022.09.040 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001959.pica (DE-627)ELV059447508 (ELSEVIER)S0168-3659(22)00635-6 DE-627 ger DE-627 rakwb eng 610 VZ 670 VZ 35.80 bkl Lee, Jong Won verfasserin aut Molecularly engineered siRNA conjugates for tumor-targeted RNAi therapy 2022transfer abstract 14 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier RNA interference (RNAi) is a major cellular mechanism regulating gene expression in which short double-stranded RNA molecules called small interfering RNA (siRNA) mediate sequence-specific mRNA degradation. RNAi technology has recently emerged as a promising therapeutic platform for the effective treatment of various diseases caused by inappropriate gene activity, such as cancer. However, the clinical translation of siRNA therapeutics has been hampered by the major hurdles associated with biological instability and limited delivery efficiency. Based on the various efforts, recent siRNA delivery strategies using cationic lipids and polymers allowed to enhance pharmacokinetics and delivery efficiency, resulting in potent and liver-targeted RNAi therapy. However, non-specific protein adsorption, high liver accumulation, and severe toxicity of cationic nanocarriers still limit the possibility of transfer of siRNA therapeutics from the laboratory to the clinic. One of the promising delivery strategies to overcome the limitations of siRNA therapeutics is carrier-free bioconjugation which is chemically modified and connected with biocompatible molecules such as lipids, peptides, antibodies, aptamers, and polymers. These molecularly engineered siRNA conjugates can be utilized for RNAi delivery to tissues beyond the liver, providing opportunities for clinical translation. This review focused on introducing the recent progress in molecularly engineered siRNA conjugates and their applications toward overcoming the limitations of siRNA for tumor-targeted delivery and therapy. RNA interference (RNAi) is a major cellular mechanism regulating gene expression in which short double-stranded RNA molecules called small interfering RNA (siRNA) mediate sequence-specific mRNA degradation. RNAi technology has recently emerged as a promising therapeutic platform for the effective treatment of various diseases caused by inappropriate gene activity, such as cancer. However, the clinical translation of siRNA therapeutics has been hampered by the major hurdles associated with biological instability and limited delivery efficiency. Based on the various efforts, recent siRNA delivery strategies using cationic lipids and polymers allowed to enhance pharmacokinetics and delivery efficiency, resulting in potent and liver-targeted RNAi therapy. However, non-specific protein adsorption, high liver accumulation, and severe toxicity of cationic nanocarriers still limit the possibility of transfer of siRNA therapeutics from the laboratory to the clinic. One of the promising delivery strategies to overcome the limitations of siRNA therapeutics is carrier-free bioconjugation which is chemically modified and connected with biocompatible molecules such as lipids, peptides, antibodies, aptamers, and polymers. These molecularly engineered siRNA conjugates can be utilized for RNAi delivery to tissues beyond the liver, providing opportunities for clinical translation. This review focused on introducing the recent progress in molecularly engineered siRNA conjugates and their applications toward overcoming the limitations of siRNA for tumor-targeted delivery and therapy. Choi, Jiwon oth Choi, Yeonho oth Kim, Kwangmeyung oth Yang, Yoosoo oth Kim, Sun Hwa oth Yoon, Hong Yeol oth Kwon, Ick Chan oth Enthalten in Elsevier Moschini, M. ELSEVIER 537 Early, intermediate and late recurrence after radical cystectomy due to bladder cancer: The necessity of a tailored follow up 2015 official journal of the Controlled Release Society and of the Japanese Society of Drug Delivery Systems New York, NY [u.a.] (DE-627)ELV012920894 volume:351 year:2022 pages:713-726 extent:14 https://doi.org/10.1016/j.jconrel.2022.09.040 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_22 GBV_ILN_40 GBV_ILN_105 35.80 Makromolekulare Chemie VZ AR 351 2022 713-726 14 |
allfieldsGer |
10.1016/j.jconrel.2022.09.040 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001959.pica (DE-627)ELV059447508 (ELSEVIER)S0168-3659(22)00635-6 DE-627 ger DE-627 rakwb eng 610 VZ 670 VZ 35.80 bkl Lee, Jong Won verfasserin aut Molecularly engineered siRNA conjugates for tumor-targeted RNAi therapy 2022transfer abstract 14 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier RNA interference (RNAi) is a major cellular mechanism regulating gene expression in which short double-stranded RNA molecules called small interfering RNA (siRNA) mediate sequence-specific mRNA degradation. RNAi technology has recently emerged as a promising therapeutic platform for the effective treatment of various diseases caused by inappropriate gene activity, such as cancer. However, the clinical translation of siRNA therapeutics has been hampered by the major hurdles associated with biological instability and limited delivery efficiency. Based on the various efforts, recent siRNA delivery strategies using cationic lipids and polymers allowed to enhance pharmacokinetics and delivery efficiency, resulting in potent and liver-targeted RNAi therapy. However, non-specific protein adsorption, high liver accumulation, and severe toxicity of cationic nanocarriers still limit the possibility of transfer of siRNA therapeutics from the laboratory to the clinic. One of the promising delivery strategies to overcome the limitations of siRNA therapeutics is carrier-free bioconjugation which is chemically modified and connected with biocompatible molecules such as lipids, peptides, antibodies, aptamers, and polymers. These molecularly engineered siRNA conjugates can be utilized for RNAi delivery to tissues beyond the liver, providing opportunities for clinical translation. This review focused on introducing the recent progress in molecularly engineered siRNA conjugates and their applications toward overcoming the limitations of siRNA for tumor-targeted delivery and therapy. RNA interference (RNAi) is a major cellular mechanism regulating gene expression in which short double-stranded RNA molecules called small interfering RNA (siRNA) mediate sequence-specific mRNA degradation. RNAi technology has recently emerged as a promising therapeutic platform for the effective treatment of various diseases caused by inappropriate gene activity, such as cancer. However, the clinical translation of siRNA therapeutics has been hampered by the major hurdles associated with biological instability and limited delivery efficiency. Based on the various efforts, recent siRNA delivery strategies using cationic lipids and polymers allowed to enhance pharmacokinetics and delivery efficiency, resulting in potent and liver-targeted RNAi therapy. However, non-specific protein adsorption, high liver accumulation, and severe toxicity of cationic nanocarriers still limit the possibility of transfer of siRNA therapeutics from the laboratory to the clinic. One of the promising delivery strategies to overcome the limitations of siRNA therapeutics is carrier-free bioconjugation which is chemically modified and connected with biocompatible molecules such as lipids, peptides, antibodies, aptamers, and polymers. These molecularly engineered siRNA conjugates can be utilized for RNAi delivery to tissues beyond the liver, providing opportunities for clinical translation. This review focused on introducing the recent progress in molecularly engineered siRNA conjugates and their applications toward overcoming the limitations of siRNA for tumor-targeted delivery and therapy. Choi, Jiwon oth Choi, Yeonho oth Kim, Kwangmeyung oth Yang, Yoosoo oth Kim, Sun Hwa oth Yoon, Hong Yeol oth Kwon, Ick Chan oth Enthalten in Elsevier Moschini, M. ELSEVIER 537 Early, intermediate and late recurrence after radical cystectomy due to bladder cancer: The necessity of a tailored follow up 2015 official journal of the Controlled Release Society and of the Japanese Society of Drug Delivery Systems New York, NY [u.a.] (DE-627)ELV012920894 volume:351 year:2022 pages:713-726 extent:14 https://doi.org/10.1016/j.jconrel.2022.09.040 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_22 GBV_ILN_40 GBV_ILN_105 35.80 Makromolekulare Chemie VZ AR 351 2022 713-726 14 |
allfieldsSound |
10.1016/j.jconrel.2022.09.040 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001959.pica (DE-627)ELV059447508 (ELSEVIER)S0168-3659(22)00635-6 DE-627 ger DE-627 rakwb eng 610 VZ 670 VZ 35.80 bkl Lee, Jong Won verfasserin aut Molecularly engineered siRNA conjugates for tumor-targeted RNAi therapy 2022transfer abstract 14 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier RNA interference (RNAi) is a major cellular mechanism regulating gene expression in which short double-stranded RNA molecules called small interfering RNA (siRNA) mediate sequence-specific mRNA degradation. RNAi technology has recently emerged as a promising therapeutic platform for the effective treatment of various diseases caused by inappropriate gene activity, such as cancer. However, the clinical translation of siRNA therapeutics has been hampered by the major hurdles associated with biological instability and limited delivery efficiency. Based on the various efforts, recent siRNA delivery strategies using cationic lipids and polymers allowed to enhance pharmacokinetics and delivery efficiency, resulting in potent and liver-targeted RNAi therapy. However, non-specific protein adsorption, high liver accumulation, and severe toxicity of cationic nanocarriers still limit the possibility of transfer of siRNA therapeutics from the laboratory to the clinic. One of the promising delivery strategies to overcome the limitations of siRNA therapeutics is carrier-free bioconjugation which is chemically modified and connected with biocompatible molecules such as lipids, peptides, antibodies, aptamers, and polymers. These molecularly engineered siRNA conjugates can be utilized for RNAi delivery to tissues beyond the liver, providing opportunities for clinical translation. This review focused on introducing the recent progress in molecularly engineered siRNA conjugates and their applications toward overcoming the limitations of siRNA for tumor-targeted delivery and therapy. RNA interference (RNAi) is a major cellular mechanism regulating gene expression in which short double-stranded RNA molecules called small interfering RNA (siRNA) mediate sequence-specific mRNA degradation. RNAi technology has recently emerged as a promising therapeutic platform for the effective treatment of various diseases caused by inappropriate gene activity, such as cancer. However, the clinical translation of siRNA therapeutics has been hampered by the major hurdles associated with biological instability and limited delivery efficiency. Based on the various efforts, recent siRNA delivery strategies using cationic lipids and polymers allowed to enhance pharmacokinetics and delivery efficiency, resulting in potent and liver-targeted RNAi therapy. However, non-specific protein adsorption, high liver accumulation, and severe toxicity of cationic nanocarriers still limit the possibility of transfer of siRNA therapeutics from the laboratory to the clinic. One of the promising delivery strategies to overcome the limitations of siRNA therapeutics is carrier-free bioconjugation which is chemically modified and connected with biocompatible molecules such as lipids, peptides, antibodies, aptamers, and polymers. These molecularly engineered siRNA conjugates can be utilized for RNAi delivery to tissues beyond the liver, providing opportunities for clinical translation. This review focused on introducing the recent progress in molecularly engineered siRNA conjugates and their applications toward overcoming the limitations of siRNA for tumor-targeted delivery and therapy. Choi, Jiwon oth Choi, Yeonho oth Kim, Kwangmeyung oth Yang, Yoosoo oth Kim, Sun Hwa oth Yoon, Hong Yeol oth Kwon, Ick Chan oth Enthalten in Elsevier Moschini, M. ELSEVIER 537 Early, intermediate and late recurrence after radical cystectomy due to bladder cancer: The necessity of a tailored follow up 2015 official journal of the Controlled Release Society and of the Japanese Society of Drug Delivery Systems New York, NY [u.a.] (DE-627)ELV012920894 volume:351 year:2022 pages:713-726 extent:14 https://doi.org/10.1016/j.jconrel.2022.09.040 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_22 GBV_ILN_40 GBV_ILN_105 35.80 Makromolekulare Chemie VZ AR 351 2022 713-726 14 |
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Enthalten in 537 Early, intermediate and late recurrence after radical cystectomy due to bladder cancer: The necessity of a tailored follow up New York, NY [u.a.] volume:351 year:2022 pages:713-726 extent:14 |
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RNA interference (RNAi) is a major cellular mechanism regulating gene expression in which short double-stranded RNA molecules called small interfering RNA (siRNA) mediate sequence-specific mRNA degradation. RNAi technology has recently emerged as a promising therapeutic platform for the effective treatment of various diseases caused by inappropriate gene activity, such as cancer. However, the clinical translation of siRNA therapeutics has been hampered by the major hurdles associated with biological instability and limited delivery efficiency. Based on the various efforts, recent siRNA delivery strategies using cationic lipids and polymers allowed to enhance pharmacokinetics and delivery efficiency, resulting in potent and liver-targeted RNAi therapy. However, non-specific protein adsorption, high liver accumulation, and severe toxicity of cationic nanocarriers still limit the possibility of transfer of siRNA therapeutics from the laboratory to the clinic. One of the promising delivery strategies to overcome the limitations of siRNA therapeutics is carrier-free bioconjugation which is chemically modified and connected with biocompatible molecules such as lipids, peptides, antibodies, aptamers, and polymers. These molecularly engineered siRNA conjugates can be utilized for RNAi delivery to tissues beyond the liver, providing opportunities for clinical translation. This review focused on introducing the recent progress in molecularly engineered siRNA conjugates and their applications toward overcoming the limitations of siRNA for tumor-targeted delivery and therapy. |
abstractGer |
RNA interference (RNAi) is a major cellular mechanism regulating gene expression in which short double-stranded RNA molecules called small interfering RNA (siRNA) mediate sequence-specific mRNA degradation. RNAi technology has recently emerged as a promising therapeutic platform for the effective treatment of various diseases caused by inappropriate gene activity, such as cancer. However, the clinical translation of siRNA therapeutics has been hampered by the major hurdles associated with biological instability and limited delivery efficiency. Based on the various efforts, recent siRNA delivery strategies using cationic lipids and polymers allowed to enhance pharmacokinetics and delivery efficiency, resulting in potent and liver-targeted RNAi therapy. However, non-specific protein adsorption, high liver accumulation, and severe toxicity of cationic nanocarriers still limit the possibility of transfer of siRNA therapeutics from the laboratory to the clinic. One of the promising delivery strategies to overcome the limitations of siRNA therapeutics is carrier-free bioconjugation which is chemically modified and connected with biocompatible molecules such as lipids, peptides, antibodies, aptamers, and polymers. These molecularly engineered siRNA conjugates can be utilized for RNAi delivery to tissues beyond the liver, providing opportunities for clinical translation. This review focused on introducing the recent progress in molecularly engineered siRNA conjugates and their applications toward overcoming the limitations of siRNA for tumor-targeted delivery and therapy. |
abstract_unstemmed |
RNA interference (RNAi) is a major cellular mechanism regulating gene expression in which short double-stranded RNA molecules called small interfering RNA (siRNA) mediate sequence-specific mRNA degradation. RNAi technology has recently emerged as a promising therapeutic platform for the effective treatment of various diseases caused by inappropriate gene activity, such as cancer. However, the clinical translation of siRNA therapeutics has been hampered by the major hurdles associated with biological instability and limited delivery efficiency. Based on the various efforts, recent siRNA delivery strategies using cationic lipids and polymers allowed to enhance pharmacokinetics and delivery efficiency, resulting in potent and liver-targeted RNAi therapy. However, non-specific protein adsorption, high liver accumulation, and severe toxicity of cationic nanocarriers still limit the possibility of transfer of siRNA therapeutics from the laboratory to the clinic. One of the promising delivery strategies to overcome the limitations of siRNA therapeutics is carrier-free bioconjugation which is chemically modified and connected with biocompatible molecules such as lipids, peptides, antibodies, aptamers, and polymers. These molecularly engineered siRNA conjugates can be utilized for RNAi delivery to tissues beyond the liver, providing opportunities for clinical translation. This review focused on introducing the recent progress in molecularly engineered siRNA conjugates and their applications toward overcoming the limitations of siRNA for tumor-targeted delivery and therapy. |
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Molecularly engineered siRNA conjugates for tumor-targeted RNAi therapy |
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Choi, Jiwon Choi, Yeonho Kim, Kwangmeyung Yang, Yoosoo Kim, Sun Hwa Yoon, Hong Yeol Kwon, Ick Chan |
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