RIBOZYME AND OMICS
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Wins Most Promising Gene Therapy Pipeline Award at International Events for the
second consecutive year
of CGTWA 2023Rznomics
announced on the 18th that it has won the Most Promising Pipeline Award in the
gene therapy category at the ‘Asia Pacific Cell & Gene Therapy Excellence
Awards (ACGTEA)’ at the ‘Cell & Gene Therapy World Asia 2023 (CGTWA 2023)’
held in Singapore. It has been awarded for the second consecutive year since
CGTWA is an event that shares representative
technologies of cell and gene therapy products of pharmaceutical and biotechnology
companies based in the Asia-Pacific region.
Through this award ceremony, Rznomics introduced
the status of trans-splicing ribozyme-based gene therapy platform technology
and circular RNA technology. The company's circular RNA technology has been
applied for international patents(PCT) and patents in major countries including
the United States, after securing pipelines and domestic original patent
Last year, Rznomics received clinical approval
for liver cancer treatment from the Korean Ministry of Food and Drug Safety and
the U.S. Food and Drug Administration (FDA). Phase 1 clinical trials of
"RZ-001" are being conducted at five hospitals in Korea. In the
future, phase 2 clinical trials will be conducted simultaneously in Korea and
the United States.
In addition, it received clinical approval
from the Korean Ministry of Food and Drug Safety and FDA in May this year for
glioblastoma treatment. It plans to conduct clinical trials within this year. Rznomics
also plans to apply for clinical trials early next year for autosomal dominant retinitis
pigmentosa, which currently has no treatment at all.
Seong-wook Lee, CEO of Rznomics, said,
"The award for the second consecutive year will be an opportunity to
recognize and promote Rznomics' technology more widely. We will do our best to
implement Rznomics' technology as an innovative treatment that can solve the
unmet demand for rare and incurable diseases."
SEONGNAM, South Korea, Aug. 3, 2023 /PRNewswire/ -- Rznomics developed a novel platform technology termed 'self-circularized RNA structure' that can efficiently and simply generate circular RNA and overcome the limitations of existing technology. Rznomics published an article regarding its development strategy and efficacy in the journal 'Molecular Therapy Nucleic Acids.'Since the success of the COVID-19 vaccine, mRNA technology has been studied with great interest in various fields, such as vaccines and therapeutics. However, conventional linear mRNA is vulnerable to nucleases, and patent-protected modified nucleic acids need to be used for efficient protein expression with the reduction of unwanted immune responses.To overcome the drawbacks of the conventional linear RNAs mentioned above, circular RNA structure technology has recently attracted attention. Circular RNA (circRNA) has a closed structure, so it has great stability against nucleases, and it has been reported that there are no influences on unwanted immune responses and protein expression without using the modified nucleotides. Therefore, if it is commercialized, circRNA vaccines or therapeutics will potentially be more competitive in price and will have the same efficacy equivalent to linear RNA in a smaller amount.Attracting large-scale investments, a couple of major biotech companies in the U.S. lead the circRNA R&D industry and show the expectations from the market. In the case of one of these companies, they use a circRNA manufacturing technology based on group I intron ribozyme, called the Permuted Intron-Exon (PIE) method. The PIE method splits the ribozyme, which was used in the cis-splicing reaction to remove the intron and link the flanking exons, into half and connects each half of ribozyme to both ends of the GOI (Gene of interest) to make the circRNA with specific GOI. Since the immaturity stage of the circRNA field, there are rooms for biotech companies to enter the competition. However, to enter the market with competitiveness, the core & innovative platform technology that overcomes the limitations of existing technologies is essential.Rznomics has developed a new circular RNA manufacturing technology that uses group I intron ribozyme as well. However, the technology is fundamentally different from the PIE method in the circularization mechanism. Rznomics has recently published its own circular RNA technology on line in Molecular Therapy Nucleic Acids (DOI: https://doi.org/10.1016/j.omtn.2023.07.034, Title; Efficient circular RNA engineering by end-to-end self-targeting and splicing reaction using Tetrahymena ribozyme), the official journal of the American Society for Gene and Cell Therapy (ASGCT). Rznomics applied its unique Tetrahymena trans-splicing ribozyme platform technology to effectively convert linear RNA into circular RNA by designing end-to-end self-targeting and splicing (STS) reaction. As shown in the figure, an RNA construct was designed to connect the GOI at the end of the group I intron ribozyme. In this construct, the target site that can be targeted by ribozyme and IGS (Internal Guide Sequence) that guides the targeted trans-ligation by base-pairing with the target site were designed to locate at both ends to enable the circular RNA formation through a self-circularization reaction.The most notable point is that in contrast to the PIE method, Rznomics' circularization technology does not leave traces of non-necessary genetic information in the GOI (Gene of Interest) after the self-circularization reaction. In the case of PIE, the ribozyme needs to connect both ends of the GOI harboring extraneous specific nucleotide sequences to form a circular RNA. Whereas, in the case of STS reaction, the ribozyme leads to self-circularization by designing any target sequence present in GOI to be located at the end of GOI.Also, Rznomics confirmed that circularization efficiency is comparable to the efficiency of the PIE method. In addition, due to the nature of the STS reaction, it is possible to establish various optimization strategies to increase the self-circularization efficiency, unlike the PIE method. It is considered that the self-circularization efficiency decreases as the length of the gene of interest. However, in the case of Rznomics technology, it is possible to screen an optimal target sequence that maximizes the efficacy of self-circularization. Rznomics stated that, through the STS-based reaction, long RNA such as human dystrophin RNA (11,265 nucleotides) was successfully self-circularized.Moreover, a self-circularization reaction occurs simultaneously during in vitro transcription which is the process of synthesizing RNA. Therefore, the purification process can be directly initiated without any additional steps of the process. In the published paper, Rznomics also mentioned a method for purifying the circRNA using the IP-RP HPLC technique. The purified circRNA with unmodified nucleotides enabled more efficient and sustained protein expression without unwanted immune responses, compared with linear RNA with modified nucleotides.This research was conducted with the support of the Ministry of Science & ICT and the National Research Foundation of Korea. The 'Self-circularization RNA structure and Platform technology' is a patent granted in South Korea (10-2442946) and has been applied in the U.S. and major countries.
Which domestic startup was selected by a
world-renowned academic journal?
Introduces RNA editing.
Explanation of technology
of 'Rznomics', a bio company
RNA replacement technology
enters clinical trials for liver cancer candidates.
In the newly emerging RNA
editing technology sector following gene editing technology, Korean
startups are receiving good reviews based on their advanced technology.
In March, the
world-renowned scientific journal, “Nature Biotechnology”, introduced
the technology of Korean venture company Rznomics in detail in an article introducing
RNA editing technology.
All living things are made
up of DNA. DNA consists of a list of four bases: adenine (A), guanine (G),
cytosine (C), and thymine (T), which go through RNA to produce proteins
necessary for life phenomena. Scientists are continuing their efforts to
develop a technology that cuts and attaches RNA, following DNA editing, and to
use it for new drug development of new drugs. In particular, unlike DNA
editing, most RNA editing technologies do not use external proteins in the
editing process, so it is expected that there will be few side effects to the
introduced in its March issue, "RNA editing technology is gaining
popularity quickly because it is transient and reversible, and is attracting
attention as a more flexible approach to editing technology compared to DNA
editing technology." Nature Biotechnology introduced major
pharmaceutical-bio companies around the world based on RNA editing technology,
mentioning the history and technology of Rznomics in Korea.
"Dr. Seong-wook Lee, a post-doctoral researcher at Duke University's Bruce
Sullenger's lab, went back to Korea and continued RNA editing research to start
Rznomics," Nature Biotechnology said. "Rznomics' new drug RZ-001 has
been approved by the U.S. Food and Drug Administration (FDA) to conduct U.S.
clinical trials for liver cancer." And added, "The candidate
substance is already undergoing clinical trials."
Founded in August 2017 by
CEO Seong-wook Lee, Rznomics' technology is "RNA replacement"
technology. Existing RNA editing techniques have only modified specific bases,
but Rznomics' editing technology can cut a specific RNA and replace the entire
cut target site with therapeutic RNA at the same time.
If the existing base
editing technology corrects the typos, the replacement technology of Rznomics
will rewrite the wrong sentence itself into a new sentence. Using this
technology, it has the advantage of being able to treat diseases with various
mutations for each patient with one drug.
RZ-001, Rznomics' liver
cancer treatment candidate, works by removing RNA that affects cancer cell
division and proliferation and replacing it with RNA that attacks cancer cells
instead to induce suicide. This can not only inhibit cancer cell proliferation
but also induce an immune response to cancer. Seong-wook Lee, CEO of Rznomics,
said, "We are targeting glioblastoma after liver cancer," adding,
"We expect to apply various intractable and rare cancers, genetic retinal
diseases, and Alzheimer's in the future."
Last year, Rznomics
received clinical approval for liver cancer from the Ministry of Food and Drug Safety and FDA and
is conducting phase 1 clinical trials of RZ-001 at five major domestic
phase 2 clinical trials will be conducted simultaneously in Korea and the
United States. It also conducted clinical applications for malignant brain
tumors and received clinical approval from the Ministry of Food and Drug Safety
and FDA in May this year, and plans to conduct clinical trials within this year.
Rznomics received a cumulative investment of 60.9 billion won, including Series
C last year, from Korea Development Bank, AON Investment, Partners Investment,
IBK Capital, Quad Ventures, SBI Investment, Shinhan Venture Investment, UTC
Investment, Samsung Securities etc. Rznomics plan to apply for technical
evaluation in the second half of this year and request a preliminary review of
KOSDAQ listing in the first half of next year.
domestic and international technologies for 'RNA and gene therapy' announced at
KMB on the 22nd
[KMB 2023] A session of 'RNA and gene therapy'
co-hosted by Rznomics will be held..Four speakers, including CEO Seong-wook
Lee, Professor Hyuk-jin Lee, and CEO Dong-ki Lee, will be announced
There will be a place to see the development
of new drugs for RNA and gene therapy in Korea, including RNA interference (RNA
interference), lipid nanoparticles (LNP), RNA-splicing ribozyme, and RNA
aptamer. Rznomics will co-host the "RNA and Gene Therapy" session on
the 22nd at the Korea Microbiological Biotechnology Association (KMB 2023) held
as an international symposium to commemorate the 50th anniversary of its
foundation at the Gyeongju Hwabaek Center for three days from the 21st. In this
session, Bruce Sullenger, a professor at Duke University, and researchers above
Dong-ki Lee's Olix Pharmaceutical are expected to participate in the session to
share innovative research results and the latest knowledge. The first speaker,
Professor Bruce Sullenger, is a professor of surgery at Duke University's
University of Medicine in the U.S. and vice chairman of the recently
established Society for RNA Therapeutics. Professor Sullenger has been
developing nucleic acid treatments for cardiovascular disease, stroke, and
cancer treatment for more than 30 years in the field of RNA treatments.
At this conference, Professor Sullenger will
present preclinical and clinical resistance data of nuclease-resistive
modulated RNA aptamer (BB-301) that binds to VWF (Won Willebrand Factor) as a
treatment target for acute ischemic stroke (AIS) diseases.
So far, the only AIS treatment approved by the
U.S. Food and Drug Administration (FDA) is the rtPA (recombinant tissue
plasminogen activator), and it is limitedly used within 4.5 hours of stroke due
to the risk of causing cerebral hemorrhage. rtPA administration is limited to
patients within 6% of the total. Among them, the role of VWF in the overall
blood clot process has recently been revealed.
speaker, CEO Seong-wook Lee, is a professor of bio-convergence engineering at
Dankook University and served as the president of the Korean Nuclear Acid
Society and the Korean Genetic Cell Therapy Society. CEO Lee is a leading
researcher in the field of trans-splicing ribozyme technology, and has been
researching the field for more than 20 years to optimize the technology, and
based on this, he founded Rznomics.
will announce the development of rare incurable treatments such as cancer,
degenerative and genetic diseases, and the results of preclinical candidates
for new drugs based on RNA replacement enzymes. RNA replacement enzyme
technology is a concept that removes target RNA while expressing a therapeutic
Rznomics was approved by the FDA and the Ministry of Food and Drug Safety to
develop phase 1/2a of the RNA replacement enzyme candidate "RZ001"
for liver cancer patients, and in May this year, it was approved to expand the
adaptation to glioblastoma. RZ-001 is a mechanism that targets telomerase
(hTERT) RNA that is specifically expressed by cancer cells by delivering
ribonucleic acid replacement enzymes to adenovirus vectors and at the same time
expresses genes that induce anticancer action.
second half of this year, Rznomics plans to submit a clinical trial plan (IND)
for phase 2 clinical trials to evaluate the effect of RZ-001 and immuno-cancer
drugs in liver cancer and "RZ-004," a candidate for retinitis
pigmentationosa (RP) treatment, an ophthalmic genetic disease.
Lee, CEO of Rznomics, said, "I recently participated in conferences and
business conferences such as the American Society for Gene Cell Therapy
(ASGCT), the American Society for Clinical Oncology (ASCO), and BIOUS. I hope
this will serve as an opportunity to seek international industry-academic
cooperation and development."
Rznomics to hold
international symposium at Korea Microbiological Biotechnology Association.Rznomics announced
on the 20th that it will participate in the International Academic Conference
of the Korea Microbiological Biotechnology Association, which will be held at
the Gyeongju Hwabaek Center for three days from the 21st. The conference will
be held in the form of international symposiums and regular conferences to
commemorate the 50th anniversary of the conference, and it is expected to be a
venue for academic exchanges to share innovative research results and latest
Rznomics plans to co-host a session of one of the
international symposiums with the academic society on the 22nd. The theme of
the session is "RNA gene therapy," which is drawing attention as a
state-of-the-art bio-new drug field, and consists of presentations from
domestic and foreign experts such as Bruce Sullenger, Duke University professor,
Dong-ki Lee, Ewha Womans University professor Hyuk-jin Lee, and Rznomics CEO Seong-wook
The first speaker, Professor Sullenger, is currently serving
as vice president of the recently established International Society for RNA
Therapy. The conference will present the results of preclinical and phase 1
clinical studies related to acute ischemic stroke (AIS) disease. CEO Dong-ki Lee
is a professor of chemistry at Sungkyunkwan University and is developing RNA
treatments based on RNA interference technology by establishing Orix based on
RNA interference (RNAi) technology. Professor Hyuk-jin Lee is a professor of
pharmacy at Ewha Womans University and is actively engaged in research in the
field of target lipid nanoparticles.
CEO Seong-wook Lee, a professor of bio-convergence
engineering at Dankook University, is a leading researcher in the field of RNA
replacement enzyme technology and has been researching the field for more than
20 years to optimize the technology. Genetic treatments for rare and intractable
diseases such as anticancer, degenerative and genetic diseases are being
developed, and the conference will introduce RNA editing technologies based
on RNA replacement enzymes and announce the development status and preclinical
Rznomics has an RNA replacement enzyme platform technology
that can remove target RNA and simultaneously express therapeutic genes. It has
secured various pipelines such as anticancer drugs, Alzheimer's, hereditary
retinal biodegradation, and Rhett's syndrome, and plans to continue expanding
into new intractable disease areas. Rznomics was recently introduced as a major
organization related to RNA editing in the famous scientific journal Nature
Seong-wook Lee, CEO of Rznomics, said, "I recently
participated in conferences and business conferences such as the American
Society for Gene Cell Therapy (ASGCT), the American Society for Clinical
Oncology (ASCO), and BIOUS. I hope this will serve as an opportunity for
international industry-academic cooperation and development."
Rznomics Cooperates with
Chungbuk National University Veterinary college to Develop Treatment for
Intractable Diseases.Collaboration throughout
preclinical research using RNA-based technologyRznomics
announced on the 1st that it has signed a business agreement with Chungbuk
National University Veterinary College to develop a treatment for incurable
diseases using ribonucleic acid (RNA)-based technology.
The two organizations decided to cooperate in preclinical
research to develop gene therapy. Academic human and material resources will be
exchanged for research on animal models for intractable diseases and
preclinical treatment for effectiveness and safety verification.
Sang-hwan Hyun, dean of Chungbuk National University's
College of Veterinary Medicine, said, "We hope that the joint R&D of
RNA-based gene therapy with a new mechanism will contribute to providing new treatment
opportunities to patients with intractable diseases with high medical demand."
"We will combine Rznomics's next-generation RNA-based
platform technology with experience in basic and preclinical research at
Chungbuk National University's veterinary college," said Sung-woo Hong,
vice president of Rznomics.
Approves Phase 1 and 2a Clinical Trials for Glioblastoma Permission granted in South Korea following the U.S.Rznomics
announced on the 25th that it received approval from the U.S. Food and Drug
Administration (FDA) for phase 1 and 2a clinical trials for glioblastoma
patients of "RZ-001" on the 6th of this month, and the same clinical
trial plan was approved by the Ministry of Food and Drug Safety.
Glioblastoma is an intractable disease with a 5-year survival
rate of less than 3%, and no clear treatment. Immuno-cancer drugs are also not
showing any effect, so a new mechanism of treatment is needed. Rznomics has a platform technology that can remove targeted
RNA and express the desired gene using a trans-splicing ribozyme. RZ-001
applied with this technology targets telomerase (hTERT) RNA, which is
specifically expressed in cancer cells, and expresses a gene that induces
anticancer action. It explained that in this process, immune cells in the body
are also induced.
Telomerase targeted by RZ-001 is expressed in most cancer
cells. Therefore, it is expected to be applicable to various carcinomas. Last
year, clinical trials for hepatocellular cancer patients were approved by the
Ministry of Food and Drug Safety and the FDA. Starting with glioblastoma, it is
pushing to expand its indication to other intractable carcinomas.In addition to anticancer drugs, it is developing treatments
in various areas such as Alzheimer's, hereditary retinal biological
degeneration, and retinal syndrome using platform technology.
"As RZ001 has been approved by Korean and U.S.
regulators for various indications, we will make all-out efforts to produce
optimal clinical results," said Sung-woo Hong, head of Rznomics'
Seong-wook Lee, CEO of Rznomics, said, "It is
encouraging to lay the foundation for glioblastoma to enter multinational
clinical trials following liver cancer," adding, "We will do our best
to provide new treatment opportunities to patients as soon as possible."
Rznomics attracted 37.2 billion won worth of Series C
investment last year. In the second half of this year, it is planning to
attract pre-IPO investment and evaluate technology.
Genetic Disease 'RNA Replacement Enzyme' 'Mutational Effect'
[ASGCT 2023] What are the main preclinical results of
"RZ-004," a candidate for autosomal dominant retinal pigment
degeneration.."It will be submitted to FDA IND at the end of this year."
Rznomics has unveiled a follow-up program following a
trans-splicing ribozyme-based anticancer drug in the initial clinical
development stage. Rznomics announced on the 23rd that it had confirmed the
effect of editing mutation-independent RNA based "RZ-004" developed
as a treatment for retinitis pigmentationosa (RP) at the American Society for
Gene Cell Therapy (ASGCT 2023) in Los Angeles.Rznomics announced the
optimization of candidate materials for RZ-004 and non-clinical results at the
ASGCT, and the presentation was conducted by Dr. Ji-hyun Kim, head of the
genetic disease task at Rznomics. Rznomics will submit a clinical trial plan
(IND) to the U.S. Food and Drug Administration (FDA) later this year to enter
clinical trials. According to Rznomics abstract information, group I
introns-based trans-splicing ribozyme, an RNA replacement enzyme, is developing
treatments using an RNA replacement mechanism. RZ-004 removes the mutated
rhodopsin RNA and operates as a mechanism to replace it with normal rhodopsin
RNA and edit it.RZ-004 was transferred to the eye via the AAV
(adeno-associated virus) vector. Rznomics has discovered the most accessible
rhodopsin RNA target site through RNA mapping in the ribozyme library. It has
been confirmed that the most efficient RNA editing occurs in the uracil (U)
base of RHO RNA 5' UTR. Rznomics also optimized ribozyme structures and
sequences to increase the trans-splying specificity and efficacy of RNA
replacement enzymes. Rznomics has identified candidates with the highest
trans-splicing editing efficiency in the in vitro cell line, and with notable
data, it has confirmed that various RHO RNA mutations are replaced by normal
(WT) RHO RNA.Rznomics delivered RZ-004 via the AAV vector to evaluate whether
it actually affects the invivo function. Rznomics delivered RZ-004 to both eyes
as a subretinal injection to the retinal pigment epithelial rat model
(P23HRHOKI). As a result, it was confirmed that the dose-dependent ERG b-wave
amplitude (amplitude) increased when RZ-004 was administered, unlike the
control group. In addition, in molecular and cell-level analysis, P23H RNA in
retinal tissue was efficiently changed to WTRHO, and the outer nuclear layer
composed of photoreceptor cells mainly targeted by ribozyme was thickened.Rznomics
also showed an electric retinal potential (ffERG) reaction when the AAV-based
RHO target ribozyme was injected under the retina in the pig model (TgP23HRHO
pig), and confirmed that the outer nuclear layer was thickened. In other words,
RZ-004 ribozyme inhibits photoreceptor degradation and maintains function in
both mouse and pig disease models, confirming the possibility of development as
a therapeutic agent. Rznomics added that it confirmed safety in primates.
Rhodopsin mutant dominant retinal pigment degeneration targeted by RZ-004 is
very demanding because there is no existing treatment, said Seong-wook Lee, CEO
of Rznomics. "We will do our best to provide innovative treatment opportunities
as soon as possible to patients suffering from vision loss."
Rznomics announces result of New Drug Pre-clinical Treatment
for Retinal Dysplasia' at American Society of Gene & Cell Therapy (ASGCT)
RNA Editing 'RZ-004' pipeline plans
To apply for FDA Clinical Trial at year-end of 2023.
Rznomics, announced on the 22nd that
it has announced the results of a pre-clinical study of its pipeline
"RZ-004," a candidate for treatment for retinal pigment degeneration,
at the American Society of Gene & Cell Therapy (ASGCT) held in Los Angeles.
RZ-004 received a lot of attention
on its potential as a new treatment through the announcement of the Association
for Research in Vision and Ophthalmology (ARVO) last month. About a month
later, the American Society of Gene & Cell Therapy selected it as oral
presentation topic. Research results such as material optimization and
pre-clinical test results have been announced.
The presentation was made by Dr.
Ji-hyun Kim, in-charge of genetic diseases at Rznomics. RZ-004 has an RNA
editing mechanism that removes mutated rhodopsin ribonucleic acid (RNA) and
replaces it with a normal rhodopsin gene be in the pre-clinical stage of completion.
Pre-clinical results that can enter clinical trials, such as efficacy, safety,
and toxicity test results confirmed by animal models with various diseases,
have been accumulated by the company.
The effectiveness was demonstrated
through electroretinogram (ERG) and optical coherence tomography (OCT). It also
confirmed safety by using rodent, pig models and non-human primates. It is
planning to apply for clinical trials with the U.S. Food and Drug
Administration (FDA) at the end of the year.
Dr. Ji-hyun Kim said, "The
results of RZ-004 were selected as the topic of oral presentation by ASGCT, the
most prestigious academic society in the field of gene and cell therapy,"
adding, "I am happy for this opportunity to announce RZ-004 to the
Seong-wook Lee, CEO of Rznomics,
said, "RZ-004's target rhodopsin mutation-mediated autosomal dominant
Retinitis Pigmentosa is very demanding because currently there is no
treatment," adding, "we will do our best to provide patients with
innovative treatment opportunities as soon as possible."