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  • LNP Application: Gene Editing Therapy
    LNP Application: Gene Editing Therapy October 12,2021.
    Lipid nanoparticles (LNP) can play an important role in gene editing therapy. IntelliaTherapeutics and Regeneron recently announced that their co-development program, ntra-2001, a systemic CRISPR/Cas9 therapy, has achieved positive results in a phase I clinical trial. A single dose of NTLA2001 resulted in an average 87% decrease in serum transthyroxine protein level (TTR), with a maximum reduction of 96% at day 28.CRISPR/Cas9 is a gene-editing tool that makes permanent, precisely targeted changes to a patient's chromosome and fixes potential genetic mutations.Ntra-2001 is a CRISPR/ CAS9-based treatment for hereditary transthyroxine protein-mediated amyloidosis with polyneuropathy (ATTRV-PN). According to Intellia Therapeutics, NTRA-2001 is a targeted delivery of LNP in humans that selectively knocks out disease-causing genes and restores necessary genetic function through targeted insertion. Three of the six patients treated in the Phase I trial received a dose of 0.1mg/kg ntLA-2001 and the other three received a dose of 0.3mg/kg NTLA2001.At day 28, TTR decreased by an average of 52% in patients receiving 0.1mg/kg and 87% in patients receiving 0.3mg/kg, with a 97% reduction in one patient. As revealed in IntelliaTherapeutics' patent, LNP contains amine lipids for encapsulation and in vivo escape, neutral and helper lipids for stabilization, and cloaking lipids. In general, LNPS used on CRISPR/Cas9 include DSPC, cholesterol, PE2K-DMG and other liposomes, which are mostly similar to those used for LNPS of mRNA vaccines. XIAMEN SINOPEG BIOTECH CO., LTD. has been developing DDS sustained-release system for more than ten years, and has strong technical reserves and experienced quality team. The high-quality polyethylene glycol derivatives developed and produced by the company have been successfully applied in the long-acting modification of PEG proteins, peptides and three types of medical devices. We also supply high purity fatty acid side chain to the market for peptide modification. In recent years, SINOPEG has turned to polyethylene glycol phospholipid, polyethylene glycol block copolymer and other high-end complex preparations, and has carried out a number of projects with domestic leading pharmaceutical enterprises. Interested friends can contact us through the following ways: US Tel: 1-844-782-5734 CHN Tel: 400-918-9898 Email: [email protected] Reference 1. Intellia Therapeutics. (2021).Source: retrieve Intellia Therapeutics: https://www.intelliatx.com/crisprcas9/types-of-edits-2/ 2.IntelliaTherapeutics(NTLA.us) and Regentium (RegN.us) announce the results of the first CRISPR clinical trial.Retrieve source: baidu: https://baijiahao.baidu.com/s?id=1703680441595581467&wfr=spider&for=pc
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  • Three-dimensional (3D) Culture of Tumor Cell Lines
    Three-dimensional (3D) Culture of Tumor Cell Lines June 25,2021.
    Despite the three-dimensional structure of tissues in vivo, the researches on the structures, functions and pathology of human tissues frequently relies on the two-dimensional (2D) model in vitro and animal model. Since the structure of monolayer in vitro model is quite different from the cell microenvironment in vivo, cell behaviors and functions, such as cell–cell interaction and cell-matrix interaction, are greatly affected. Moreover, animal model often fail to repeat the human characteristic because of species differences. Three-dimensional (3D) culture of tumor cell lines has been advocated as the alternative. It is simple and practicable and has the advantage of simulating the cell microenvironment in vivo. Matrices for 3D cell culture mimic one or more properties of the extracellular matrix (ECM) and tumor microenvironment in vivo. The 3D cell culturing matrices are generally composed of porous structures with diameter less than 300 nm, which can provide enough space for the growth of cells. The cancer cells can form 3D aggregates or spheroids inside the matrix. According to the main component, 3D cell culture matrices can be divided into two main categories: matrix based on natural materials and matrix based on synthetic materials. Matrices based on natural materials can provide a biological environment, but the mechanical performance of materials is commonly poor and the batch-to-batch discrepancy cannot be completely eliminated. Natural materials are usually used to form hydrogel composites. Synthetic scaffolds are polymers like Polyethylene glycol (PEG), Polylactide (PLA), Poly(lactide-co-glycolide) (PLGA/PLG) which are biodegradable and easy to reproduce. Among these materials, the thermogelling synthetic copolymer hydrogels with a sol-gel transition exhibit lower critical solution temperature (LCST) behavior, which is meaningful for a 3D cell culturing matrix. When the sol gel transition temperature of smart hydrogel is between 5℃ and 37℃, the matrix has advantages in further separation of materials and cell aggregates. Hydrogels have received extensive attention in tissue engineering and 3D cell culture, owing to their inherent properties such as flexible matrix, high water content, and responsive network structures. Hydrogels can be formed both chemically and physically. PEG hydrogels are excellent candidates as biomaterials because of their potential for incorporating both biophysical and biochemical cues and their prevention of non-specific protein adsorption, biocompatibility and FDA approval for use in humans. Thermo-sensitive hydrogel based on PLGA-PEG-PLGA tri-block copolymers has been used for delivery of proteins and water-insoluble drugs. The proper LCST and good biocompatibility of PLGA-PEG-PLGA tri-block copolymers make it a good choice for in vitro cell culture matrix. References 1. Caldwell A. S., Aguado B. A., Anseth K. S. Designing Microgels for Cell Culture and Controlled Assembly of Tissue Microenvironments. Adv Fu...
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  • A novel core-shell nano drug delivery system: Tumor inhibition rate up to 98%
    A novel core-shell nano drug delivery system: Tumor inhibition rate up to 98% June 1,2021.
    Cancer remains one of the most common diseases that is a threat to human health. Currently, chemotherapy is an important and indispensable strategy for treating cancer besides surgical treatment and radiotherapy. Thus, it has attracted a number of pharmaceutical researchers for the discovery and development of new anticancer drugs. Unfortunately, approximately 90% of drug candidate molecules in the discovery pipeline are poorly water soluble. Poor solubility can elicit low oral bioavailability and insufficient efficacy in vivo, and make intravenous (IV) administration challenging. Nanotechnology-based drug delivery systems, such as drug nanocrystals (NCs) and liposomes have enabled in improving the solubility and/or attained targeted delivery via the enhanced permeability and retention (EPR) effect, and/or specific ligand-mediated tumor-targeting effect. Liposome is one of the most developed nanomedicines, high stability and flexible surface modification/functionalization, have been widely used in the field of drug development. Hydrophobic drugs are mainly entrapped in the liposomes by embedding in the lipid bilayers, which usually results in a low drug loading capacity that challenges their clinical transformation. In contrast, drug NCs, a nanoscale carrier-free colloidal delivery system with a theoretical drug loading capacity of up to 100%, are quite promising for poorly water-soluble drugs. However, drug NCs still face major challenges in their stability and targeted delivery. Recently, researchers from the Chinese Academy of Sciences present a novel drug delivery strategy, called [email protected] ([email protected]), which integrates drug nanocrystals into the hydrophilic inner cores of liposomes and forms a hybrid core (nanocrystal)-shell (liposome) drug delivery system, merging the advantages of liposomes and drug nanocrystals to overcome these issues,for the targeted delivery of poorly watersoluble drugs. The performance of the proposed [email protected] delivery system was demonstrated on the drug candidate CHMFL-ABL-053 (053), which was discovered by their group. Three different 053-nanodrugs, namely 053-NC, [email protected], and [email protected], were fabricated for in vitro and in vivo evaluation. In conclusion, as a proof of concept, this study showed that [email protected] might be a potential strategy for designing nanocrystal or liposome-based drug delivery systems with high colloidal stability, high drug loading, functionalized surface, and enhanced biological effects (including PK profile, tumor cell targeting, and in vivo antitumor efficacy). Additionally, this work may promote the development of more efficient liposome-based formulations for the delivery of poorly water-soluble drugs for commercial and clinical applications. 1. Title:Nanocrystal-loaded liposome for targeted delivery of poorly water-soluble antitumor drugs with high drug loading and stability towards efficient cancer therapy 2. Author: Huamin Liang, Fengming Zou, Qingwang Liu, Beilei Wang,...
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