Tohoku University · 생화학·유전·분자생물학
Hiroki Tanaka 교수의 연구실은 주로 RNA 기반 치료제의 효율적 전달을 위한 지질 나노입자(LNP) 기반 딜리버리 시스템을 핵심으로 연구하고 있습니다. 특히 자가 분해 가능한 지질 유사 물질을 활용한 LNP 설계를 통해 세포 내 RNA 방출을 촉진하고, 암시적이고 안정적인 약물 전달을 실현하고자 합니다. mRNA 및 siRNA를 포함한 다양한 RNA 유형의 치료적 응용을 목표로 하며, 뇌 질환 치료나 유전자 치료 분야에서의 응용 가능성에도 주력하고 있습니다.
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
Abstract RNA‐based therapeutics is a promising approach for curing intractable diseases by manipulating various cellular functions. For eliciting RNA (i.e., mRNA and siRNA) functions successfully, the RNA in the extracellular space must be protected and it must be delivered to the cytoplasm. In this study, the development of a self‐degradable lipid‐like material that functions to accelerate the collapse of lipid nanoparticles (LNPs) and the release of RNA into cytoplasm is reported. The self‐deg
Gene therapy is a promising strategy for curing certain types of brain diseases. Supplementation of therapeutic proteins such as aromatic amino acid decarboxylase (AADC) or nerve growth factor (NGF) have been reported to be successful examples of such treatments. However, there are safety concerns because these systems are based on virus-based gene vectors. A safe and efficient artificial carrier is thus urgently needed as an alternative. In this study, an mRNA based artificial gene carrier was
タンパク質の導入を目的とするmessenger RNA（mRNA）やタンパク質のノックダウンを目的とするsmall interfering RNA（siRNA）を用いた医薬品が承認されたことを受け、今後RNA創薬はますます加速すると考えられる。これらの新規モダリティを基盤とした医療を実現するうえでは、脂質ナノ粒子（Lipid Nanoparticle：LNP）がそのデリバリー技術として大きく貢献している。本稿では現在までのLNPs開発の経緯について概説するとともに、mRNA医薬品の最初の例となったRNAワクチンについて、その免疫活性化機構について最近の知見を紹介する。また、今後のさらなる医療応用を加速するうえで必須となるターゲティング技術について解説する。
Abstract The oxidation of ammonium ion to nitrite and nitrate ion (nitrification) has been studied in a laboratory scale fluidized sand bed reactor with attached microbial growth. The undefined population of Nitrobacteracea organisms were immobilized on the sand particles by natural attachment after 2–3 months of adaptation. General balance equations have been formulated for a recycle reactor and oxygenation tank system. Kinetic experiments in the reactor and in a microrespirometer have been ana
The world-first success of lipid nanoparticle (LNP)-based siRNA therapeutics (ONPATTRO<sup>®</sup>) promises to accelerate developments in siRNA therapeutics/gene therapy using LNP-type drug delivery systems (DDS). In this study, we explore the optimal composition of an LNP containing a self-degradable material (ssPalmO-Phe) for the delivery of oligonucleotides. siRNA or antisense oligonucleotides (ASO) were encapsulated in LNP with different lipid compositions. The hepatic knockdown efficiency
Based on the clinical success of an <i>in vitro</i> transcribed mRNA (IVT-mRNA) that is encapsulated in lipid nanoparticles (mRNA-LNPs), there is a growing demand by researchers to test whether their own biological findings might be applicable for use in mRNA-based therapeutics. However, the equipment and/or know-how required for manufacturing such nanoparticles is often inaccessible. To encourage more innovation in mRNA therapeutics, a simple method for preparing mRNA-LNPs is prerequisite. In t
(1) Background: T cells are important target cells, since they exert direct cytotoxic effects on infected/malignant cells, and affect the regulatory functions of other immune cells in a target antigen-specific manner. One of the current approaches for modifying the function of T cells is gene transfection by viral vectors. However, the insertion of the exogenous DNA molecules into the genome is attended by the risk of mutagenesis, especially when a transposon-based gene cassette is used. Based o
An mRNA gene therapy represents a potentially promising therapeutic for curing inflammatory diseases. The transient nature of the gene expression of mRNA would be expected to be beneficial for avoiding undesired side effects. Since the mRNA is a vulnerable molecule, a development of a carrier that can deliver the mRNA to the cytoplasm has a high priority. We report herein on the development of a system for delivering mRNA to the inflammatory lesion in a dextran sulfate sodium (DSS)-induced colit
The lipid nanoparticle (LNP) is one of the promising nanotechnologies for the delivery of RNA molecules, such as small interfering RNA (siRNA) and messenger RNA (mRNA). A series of LNPs that contain an mRNA encoding the antigen protein of SARS-CoV-2 were already approved as RNA vaccines against this infectious disease. Since LNP formulations are generally metastable, their physicochemical properties are expected to shift toward a more stable state during the long-time storage of suspensions. The
RNA vaccines are applicable to the treatment of various infectious diseases via the inducement of robust immune responses against target antigens by expressing antigen proteins in the human body. The delivery of messenger RNA by lipid nanoparticles (LNPs) has become a versatile drug delivery system used in the administration of RNA vaccines. LNPs are widely considered to possess adjuvant activity that induces a strong immune response. However, the properties of LNPs that contribute to their adju
Currently, the main target of the nanocarrier-mediated siRNA delivery systems is liver. The targeting of non-hepatic tissue is the next challenge. In this case, the design of neutral particle with well-organized intracellular trafficking, as well as an identification of the promising ligand is needed.
