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Nucleic Acid Drug R&D Platform

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Medicilon nucleic acid drug R&D platform is an integrated and comprehensive solution that covers drug discovery, CMC and preclinical research services. Based on a rigorous scientific attitude, an open-minded scientific spirit and advanced equipment, our integrated solution can meet the industry's research and development needs for cutting-edge innovative nucleic acid drugs, and undertake research programs like nucleic acid drug discovery, screening and preclinical research services for pharmaceutical companies and scientific research institutions.

Medicilon nucleic acid drug R&D platform is an integrated and comprehensive solution that covers drug discovery, CMC and preclinical research services. Based on a rigorous scientific attitude, an open-minded scientific spirit and advanced equipment, our integrated solution can meet the industry's research and development needs for cutting-edge innovative nucleic acid drugs, and undertake research programs like nucleic acid drug discovery, screening and preclinical research services for pharmaceutical companies and scientific research institutions.

Popular types

ASOsiRNA  mRNA  Aptamer

Advantages

For its fast and intuitive design of base sequences, the development of nucleic acid drugs applies simple materials, convenient preparation processes and affordable production costs, which greatly shorten the drug development cycle, making it possible to customize individualized treatment plans. Hence, it offers a feasible solution for rare diseases and other problems currently plagued.

Nucleic Acid Synthesis and Chemical Modifications

Synthesis

Monomer synthesis

Oligonucleotide synthesis

Delivery system synthesis

Oligo conjugate synthesis

Modification

Sugar modification

Nucleobase modification

Backbone modification

Delivery system modification

Bioactivity Screening

Evaluation of binding between siRNA-GALNAc and targeted liver cells. (ELISA,SPR,FP,FACS, MSD, Confocal microscope)

Evaluation of decrease in target mRNA/protein level.

Evaluation of cell phenotypes and functional interfere.

Evaluation of cell phenotypes and functional interfere.

Searching for potential off-target mRNA/protein in the database, such as NCBI, nucleotideBLAST.

Overall analysis applying RNAseq or RNA Microarray.

Nucleic Acid Process R&D

Select starting materials:We aim to choose starting materials with traits like easy to purchase, mild toxicity, good quality stability;

Process R&D of nucleic acid:We aim to develop stable and green synthesis routes with low cost and high security.

Quality Control:Up-to-date quality control system with complete technical standard.

Scale up:End to end service ensuring smooth transfer.

Nucleic acid drugs preparation

Due to their low immunogenicity, biocompatibility, and high encapsulation efficiency for oligonucleotide molecules, lipids and their derivatives have become the go-to delivery systems for nucleic acid drugs that have attracted much attention in recent years. The system is positively charged in the physiological environment. The negatively charged nucleic acid molecules are encapsulated by electrostatic action, and the positively charged surface can also help the entire carrier system to combine with the cell membrane of the target cell, thereby playing a delivery role.

Common delivery systems

Medicilon’s preparation methods of nanoparticles

Traits of successful delivery systems

Easily modified, easily synthesized, easily produced.

The on-target and off-target ratio of delivery should be within an acceptable range.

The effective dose must be significantly lower than the toxic dose.

The bioactivity of the nucleic acid should be consistent from batch to batch.

In most clinical cases, repeated administration does not result in loss of efficacy or safety.

Medicilon’s nanoparticle R&D lab

Nucleic acid-lipid system R&D

Formulation: drug to lipid ratio, solvent screening, aqueous to organic solvent ratio

Process: Preparation methods

Stability

Dosage form screening

Nucleic acid drugs bioanalysis

PK/TK analysis

H-ELISA LC-MS/MS;

H-ECL;

RT-qPCR;

qPCR;

ddPCR

ADA analysis

Total ADA;

MSD ;

Nab analysis: CLBA or cell-based assay

PD or TOX related cytokines & biomarkers

Cytokine&Biomarker

Singleplex;

Multiplex (Luminex, MSD, FACS CBA)

FACS

Solutions for Nucleic acid bioanalysis

LC-MS/MS/HRMS Platform

High specificity

High sensitivity: ng level

Advantages: end product detectable

Hybridization-EIA/ECL Platform

High specificity

Sensitivity: Detectable within 1 log copy

Advantage:More Sensitive

qPCR/ddPCR Platform

Sensitivity: pM level

Advantages: variable marking strategy; personalized reaction strategy.

Pharmacology evaluation

Contrast of different drug delivery methods.

Relevance analysis between pharmacology and target mRNA/protein degradation & nucleic acid drug PK

Animals: Female BALB/c Nude mice;

Cells: MDA-MB-231, 5*106/mouse;

Model Establishment: Right flank SC injection;

Treatment: IV injection;

TIW (three times a week);

Group3, 4: mRNA (LNP)group.

Animals: Female BALB/c Nude mice;

Cells: MDA-MB-231, 5*106/mouse;

Model Establishment: Right flank SC injection;

Treatment: Intratumor in-jection;

TIW (three times aweek);

Group 7, 8: mRNA(LNP) group.

Dendrimer LNP

Luc mRNA;Ⅳ and intra-tumoral

CNP-generated exosome

Delivery of PTEN mRNA by Glioma-directed Exosome EXO-T,IV

Syngeneic mouse models

Cancer Type Cell Lines
Bladder Cancer MB49
Brain Cancer G261
Breast Cancer 4T1, EMT6, JC,EO771
Colon Cancer CT26.WT, MC-38, Colon26
Leukemia C1498, L1210, WEHI-3
Liver cancer H22, Hepa 1-6
Lung Cancer LLC1, KLN205
Lymphoma A20, EL4,  L5178-R, E.G7-OVA
Mastocytoma P815
Melanoma B16-F10, Clone-M3
Myeloma J558
Pancreas Cancer Panc 02
Renal Cancer RENCA
Luciferase Cell Line
G261-luc, 4T1-luc, Mc38-luc, H22-luc, B16-F10-luc, LLC1-luc

Humanized mouse models

Cancer Type Cell Lines in PBMC or HSC CD34+ Humanized Mice
Brain Cancer U-87 MG
Breast Cancer HCC1954, MDA-MB-231, JIMT-1
Colon Cancer HT29, LoVo, Ls174T, HT-15
Gastric Cancer NCI-N87, NUGC-4
Leukemia THP-1
Lung Cancer HCC827, NCI-H1975, NCI-H292, A549
Lymphoma Raji, TMD8, MOLM-13
Melanoma A375
Myeloma RPMI-8226, NCI-H929, MM.1S
Ovarian Cancer OVCAR-3
Pancreatic Cancer Capan-2
Renal Cancer 786-O
Skin Cancer A431

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