Three variants of minimized hepatitis delta virus (HDV) RNA ribozyme systems designed on the basis of the "pseudoknot" model were synthesized and their tertiary interactions were analyzed by NMR spectroscopy. Rz-1 is a cis-acting ribozyme system (the cleaved form, 56-mer) in which stem IV is deleted from the active domain of genomic HDV RNA. Rz-1 was uniformly labeled with stable isotopes, 13C and 15N. Rz-2 is a trans-acting ribozyme system (substrate: 8-mer, the cytidine residue at the cleavage site is replaced by 2'-O-methylcytidine; enzyme: 16-mer plus 35-mer). Rz-2 was partially labeled with stable isotopes in guanosine residues of enzyme 35mer. Rz-4 is a trans-acting ribozyme system (substrate: 8mer, the cytidine residue at the cleavage site is replaced by 2'-O-methylcytidine; enzyme 53mer) which was designed by Perrotta and Been. Rz-4 has the same sequence and an extra loop closing stem IV. From 2D-NOESY and 2D-HSQC (except for Rz-4) spectra, it was suggested each ribozyme forms "pseudoknot" type structure in solution. Additionally, it was found that G38 of Rz-1, G28 and G29 of Rz-2 and Rz-4 form base-pairs. These novel base-pairs are observed in the crystal structure of a modified genomic HDV RNA. From temperature change experiment of Rz-2, the imino proton signal of G28 disappeared at 50 degrees C earlier than the other corresponding signals. Upon MgCl2 titration of Rz-2, this signal showed the largest shift.

1999-11-01·Nucleic Acids Symposium Series

Design and NMR analysis of HDV ribozymes for structural investigation

Article

作者: Nishikawa, Fumiko ; Tanaka, Yoichiro ; Hori, Tamaki ; Katahira, Masato ; Kurihara, Yasuyuki ; Uesugi, Seiichi ; Nishikawa, Satoshi ; Fukunaga, Yurika ; Sakamoto, Taiichi

Three variants of minimized hepatitis delta virus (HDV) RNA ribozyme systems (Rz-1 to approximately Rz-3) (Fig. 1) were designed on the basis of the "pseudoknot" structure model and synthesized. Rz-1 is a cis-acting ribozyme system (a cleaved form, 56-mer) in which stem IV is deleted from the active domain of genomic HDV RNA. Rz-1 was uniformly labeled with stable isotopes, 13C and 15N. The 2D-NOESY and 2D-HSQC data for Rz-1 suggest that Rz-1 forms the pseudoknot structure and G38 which is opposite to the cleavage site makes a base-pair. Rz-2 is a trans-acting ribozyme system which consists of three RNA oligomer strands (substrate: 8-mer, the cytidine residue at the cleavage site is replaced by 2'-O-methylcytidine; enzyme: 16-mer plus 35-mer). Rz-3 is a ribozyme in which the three RNA strands of Rz-2 are connected. It turns out that Rz-3 forms an inactive structure with low cleavage activity (k(obs) = 0.009) and final cleavage yield (6%). Rz-3 has the highest cleavage activity at pH 5.5. The optimal activity at acidic pH is similar to that of the wild type ribozyme. We also synthesized and examined the activity and structure of Rz-4 (designed by Perrotta and Been) which consists of two RNA strands (1).

项与 RZ-004 相关的新闻（医药）

2024-08-05

·PRNewswire

SK pharmteco and Rznomics Explore Collaboration for RNA-based Gene Therapy Development and Manufacturing

SEONGNAM, South Korea, Aug. 5, 2024 /PRNewswire/ -- SK pharmteco, a global contract development, manufacturing, and analytical testing organization serving both the small molecule and cell & gene therapy industry, and Rznomics Inc., a South Korea-based biopharmaceutical company specializing in the development of RNA-based gene therapeutics, have signed a memorandum of understanding (MOU) for a contract development and manufacturing partnership. When finalized, the multi-year partnership will establish a strategic collaboration between SK pharmteco and Rznomics to develop and commercialize multiple gene therapy products. SK pharmteco will provide technical expertise and resources, including the facilities and personnel, to enable a smooth transition from clinical to full-scale commercial manufacturing of Rznomics' innovative ribonucleic acid (RNA)-based biopharmaceuticals. "We are thrilled about the opportunity to partner with Rznomics on their groundbreaking initiatives," said Andy Fenny, Chief Commercial Officer of SK pharmteco. "By combining our significant expertise in gene therapy manufacturing with Rznomics' innovative RNA-based therapeutic approach, we believe this collaboration has the potential to deliver life-changing treatments to patients in need quickly." Seong-Wook Lee, President and Chief Executive Officer of Rznomics, commented: "This partnership will mark late-stage development and manufacturing of our gene therapy pipeline to prepare the path towards Phase II and later stage clinical trials and potential commercialization. We look forward to working closely with SK pharmteco." About SK pharmteco SK pharmteco is a global contract development and manufacturing organization (CDMO) with 13 offices and manufacturing facilities across the U.S., Europe, and Korea. The company partners with biopharmaceutical companies of all sizes to manufacture Active Pharmaceutical Ingredients (API) and intermediates, cell and gene therapy technologies, registered starting materials, and analytical services for the biopharmaceutical industry worldwide. SK pharmteco is a subsidiary of SK Inc. (KRX: 034730) (SK), the strategic investment company for SK Group, South Korea's second-largest conglomerate. About Rznomics Rznomics is a South Korea-based innovative RNA biopharmaceutical company, with vision to treat/conquer various human intractable diseases. Rznomics has developed and focused on several pipelines with RNA editing platform technologies of RZ-001 (Hepatocellular Carcinoma, Glioblastoma), RZ-003 (Alzheimer), RZ-004 (Retinitis Pigmentosa), RZ-005 (neurodegenerative disorder) and Circular RNA platform. For RZ-001, the lead pipeline, Rznomics has received Phase I/IIa IND approvals from the FDA for Hepatocellular Carcinoma and Glioblastoma in 2022 and 2023 each. In addition, FDA has granted Fast Track Designation for GBM in November 2023 and Orphan Drug Designation for HCC in January 2024. Early-phase trials have also commenced in Korea, upon IND approval for RZ-001 from the Ministry of Food and Drug Safety (MFDS). Rznomics has received IND approval for combination of RZ-001 and Immunotherapy from the MFDS as well, in December 2023. Contact: Keith Bowermaster, APR, CCMP Communications Consultant [email protected] Website: Jihye Yang Associate Manager [email protected] Website: SOURCE Rznomics Inc.

孤儿药快速通道临床申请临床研究基因疗法

2024-07-15

·PRNewswire

Rznomics Inc. Secures Australian Clinical Trial Notification for RHO-targeted Splicing Ribozyme-based RNA Editing Therapy for Retinitis Pigmentosa

SEONGNAM, South Korea, July 15, 2024 /PRNewswire/ -- Rznomics Inc., a South Korea based biopharmaceutical company specialized in the development of RNA-based gene therapeutics, announced that it has received Clinical Trial Notification (CTN) from the Australian Therapeutic Goods Administration (TGA) for the initiation of a Phase 1/2a clinical trial evaluating RZ-004, a gene therapeutic candidate for autosomal dominant Retinitis pigmentosa with rhodopsin mutation. Retinitis pigmentosa is an inherited retinal disease in which photoreceptor cells in retina degenerates and leads to blindness. Autosomal dominant Retinitis pigmentosa is caused by numerous diverse genetic defects and mutations in rhodopsin is the most common cause of autosomal Retinitis pigmentosa. More than 150 mutation sites in rhodopsin have been identified and it causes difficulty in treating rhodopsin-mediated autosomal dominant Retinitis pigmentosa. RZ-004, AAV vector encoding a rhodopsin RNA-targeting trans-splicing ribozyme along with wild type rhodopsin, specifically targets and reprograms pathogenic mutant Rhodopsin mRNA into normal Rhodopsin mRNA, thereby leading to the therapeutic effect. Since RZ-004 targets conservative upstream region of the rhodopsin mutations, all different types of mutations in each patient could be treated with one therapy. "The Clinical Trial Notification (CTN) marks an important milestone in addressing the high unmet medical need of autosomal dominant retinitis pigmentosa with rhodopsin mutation," said Dr. Seong-Wook Lee, Chief Executive Officer of Rznomics. "Rznomics is committed to developing innovative RNA-based biopharmaceuticals for the treatment of various human rare and intractable diseases, and we look forward to the initiation of the clinical trial to evaluate the safety and efficacy profile of RZ-004 for providing a potential treatment option for patients suffering from the disease." About Rznomics Inc. Rznomics is a biopharmaceutical company founded in 2017 with the vision of developing RNA-based gene therapies for cancer and incurable diseases. Rznomics' core platform technology is RNA editing technology based on an RNA replacement enzyme, known as trans-splicing ribozyme, which can specifically target and cleave disease-causing RNA and simultaneously replace the whole part of targeted downstream RNA with therapeutic RNA to selectively and regulatedly induce therapeutic gene expression in cells expressing the target RNA. The RNA replacement enzyme platform is being developed for numerous indications such as malignant diseases including hepatocellular carcinoma and glioblastoma, retinitis pigmentosa, rett syndrome, and alzheimer's disease. For more information, please visit SOURCE Rznomics Inc.

siRNA临床研究基因疗法寡核苷酸

100 项与 RZ-004 相关的药物交易

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