Design and kinetic analysis of hammerhead ribozyme and DNAzyme that specifically cleave TEL-AML1 chimeric mRNA
- Department of Bioscience and Biotechnology, Konkuk University, 1-Hwayang-dong, Gwangjin-gu, Seoul 143-701 (Korea, Republic of)
- Nambu Blood Laboratory, Korean Red Cross, Busan 614-814 (Korea, Republic of)
- PharmcoGenomic Research Center, Inje University, Busan 614-735 (Korea, Republic of)
In order to develop the oligonucleotides to abolish an expression of TEL-AML1 chimeric RNA, which is a genetic aberration that causes the acute lymphoblastic leukemia (ALL), hammerhead ribozymes and deoxyoligoribozymes that can specifically cleave TEL-AML1 fusion RNA were designed. Constructs of the deoxyribozyme with an asymmetric substrate binding arm (Dz26) and the hammerhead ribozyme with a 4 nt-bulged substrate binding arm in the stem III (buRz28) were able to cleave TEL-AML1 chimeric RNA specifically at sites close to the junction in vitro, without cleaving the normal TEL and AML1 RNA. Single-turnover kinetic analysis under enzyme-excess condition revealed that the buRz28 is superior to the Dz26 in terms of substrate binding and RNA-cleavage. In conjunction with current progress in a gene-delivery technology, the designed oligonucleotides that specifically cleave the TEL-AML1 chimeric mRNA are hoped to be applicable for the treatment of ALL in vivo.
- OSTI ID:
- 21143863
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 374, Issue 1; Other Information: DOI: 10.1016/j.bbrc.2008.07.008; PII: S0006-291X(08)01325-9; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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