Screening of a heptamer-type sgRNA library for potential therapeutic agents against hematological malignancies.
tRNase-Z(L)-utilizing efficacious (TRUE) gene silencing is an RNA-mediated gene expression control technology that has therapeutic potential. This technology is based on the property of tRNase Z(L) that it can cleave any target RNA at any desired site under the direction of an appropriate artificial small guide RNA (sgRNA). To search for novel potential therapeutic sgRNAs for hematological malignancies, we screened a library composed of 156 sgRNAs, and found that 20 sgRNAs can efficiently induce apoptosis in leukemia and/or myeloma cells. Furthermore, we demonstrated that 4 of the 20 sgRNAs can reduce growth rates of HL60 cells in mouse xenograft models.
Department of Applied Life Sciences, Niigata University of Pharmacy and Applied Life Sciences, Higashijima 265-1, Akihaku, Niigata, Niigata 956-8603, Japan.
Masayuki
M
Takahashi
Department of Applied Life Sciences, Niigata University of Pharmacy and Applied Life Sciences, Higashijima 265-1, Akihaku, Niigata, Niigata 956-8603, Japan.
Reyad A
RA
Elbarbary
Department of Applied Life Sciences, Niigata University of Pharmacy and Applied Life Sciences, Higashijima 265-1, Akihaku, Niigata, Niigata 956-8603, Japan; Laboratory of Hematology and Oncology, Niigata University Graduate School of Health Sciences, Asahimachi-dori 746-2, Chuoku, Niigata, Niigata 951-8518, Japan.
Norihiro
N
Watanabe
Department of Applied Life Sciences, Niigata University of Pharmacy and Applied Life Sciences, Higashijima 265-1, Akihaku, Niigata, Niigata 956-8603, Japan.
Atsushi
A
Goto
Department of Applied Life Sciences, Niigata University of Pharmacy and Applied Life Sciences, Higashijima 265-1, Akihaku, Niigata, Niigata 956-8603, Japan.
Daichi
D
Kamiya
Department of Applied Life Sciences, Niigata University of Pharmacy and Applied Life Sciences, Higashijima 265-1, Akihaku, Niigata, Niigata 956-8603, Japan.
Yoshihiro
Y
Watabe
Laboratory of Hematology and Oncology, Niigata University Graduate School of Health Sciences, Asahimachi-dori 746-2, Chuoku, Niigata, Niigata 951-8518, Japan.
Takayoshi
T
Uchiyama
Laboratory of Hematology and Oncology, Niigata University Graduate School of Health Sciences, Asahimachi-dori 746-2, Chuoku, Niigata, Niigata 951-8518, Japan.
Miwako
M
Narita
Laboratory of Hematology and Oncology, Niigata University Graduate School of Health Sciences, Asahimachi-dori 746-2, Chuoku, Niigata, Niigata 951-8518, Japan.
Masuhiro
M
Takahashi
Laboratory of Biochemistry, Niigata University Graduate School of Health Sciences, Asahimachi-dori 746-2, Chuoku, Niigata, Niigata 951-8518, Japan.
Yoshiaki
Y
Takahashi
Department of Clinical Pathology, Saiseikai Niigata Daini Hospital, Terachi 280-7, Nishiku, Niigata, Niigata 950-1104, Japan.
Noriko
N
Ishihara
Biologics Research Laboratories, Kyowa Hakko Kirin Co., Ltd., Asahimachi 3-6-6, Machida, Tokyo 194-8533, Japan.
Tatsuya
T
Miyazawa
Biologics Research Laboratories, Kyowa Hakko Kirin Co., Ltd., Asahimachi 3-6-6, Machida, Tokyo 194-8533, Japan.
Tetsuo
T
Yoshida
Department of Applied Life Sciences, Niigata University of Pharmacy and Applied Life Sciences, Higashijima 265-1, Akihaku, Niigata, Niigata 956-8603, Japan; Department of Biochemistry and Molecular Biology, Hokkaido University Graduate School of Dental Medicine, North 13, West 7, Sapporo, Hokkaido 060-8586, Japan.
Mitsuoki
M
Kawano
Department of Biochemistry and Molecular Biology, Hokkaido University Graduate School of Dental Medicine, North 13, West 7, Sapporo, Hokkaido 060-8586, Japan.
Masato
M
Tamura
Department of Applied Life Sciences, Niigata University of Pharmacy and Applied Life Sciences, Higashijima 265-1, Akihaku, Niigata, Niigata 956-8603, Japan. Electronic address: mnashimoto@nupals.ac.jp.
Masayuki
M
Nashimoto
D000818:Animals; D045744:Cell Line, Tumor; D004722:Endoribonucleases / Q000235:genetics; D015723:Gene Library; D020868:Gene Silencing; D019337:Hematologic Neoplasms / Q000628:therapy*; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D058727:RNA, Small Untranslated
D004722:Endoribonucleases; C531011:tRNase Z, human; D058727:RNA, Small Untranslated
Leukemia; Multiple myeloma; RNA therapy; TRUE gene silencing; sgRNA; tRNase Z(L)