Accelerating Discovery with Smarter siRNA Solutions
SiRNA Design & Screening Platform
Overview
From Design to Discovery: siRNA Simplified
At Medicilon, our siRNA in vitro screening platform is tailored to advance RNA interference research and accelerate drug discovery. With the forefront tools and proven methodologies, we provide end-to-end solutions, from siRNA design to in vitro efficacy assessments.
Innovative siRNA Design with Medicilon
Medicilon employs advanced tools and protocols to design high-potency, low off-target siRNA sequences:
siDirect (siRNA-Design) Algorithm
Enhances targeting accuracy by integrating sequence alignment across species
Polymorphism and Conservation Analysis
Ensures efficacy across human, mouse, rat, and other analogs
Advanced Online and Manual Tools
Incorporates SNP and tissue-specific expression data for customized siRNA sequences
Off-Target Prediction
Uses alignment and mismatch scoring systems to minimize unwanted effects
Proven Success
Case Study: To develop a potent siRNA candidate for effective knockdown of Antithrombin III (ATIII) in human cells
Approach: A structured 6-step design and validation workflow:
Sequence Alignment
Ensured specificity and target match
Analog Analysis
Compared sequence variants for optimization
SNP Analysis
Screened for genetic polymorphisms to reduce variability
Tissue & Cell-Specific Expression Analysis
Verified expression patterns in Hep3B cells.
siRNA Sequence Design
Generated over 300 candidate sequences
Off-Target Screening & Lead Selection
Selected MED-A-0280 for its superior performance
REsearch and Application
In Vitro Screening Capabilities for siRNA Therapeutics
Medicilon’s robust suite of in vitro assays is tailored to evaluate efficacy, safety, and target specificity of siRNA candidates:
In Vitro Efficacy Evaluation
Understanding a comprehensive in vitro evaluation strategy to assess GalNAc-conjugated siRNA efficacy, including binding, uptake, and gene silencing assays across various cellular platforms.
GalNAc-Related Assays
- GalNAc-ASGPR1 binding via SPR and ELISA
- HepG2 cell uptake (confocal microscopy)
- HepG2 cell surface binding (FACS)
- Primary hepatocyte uptake measured by qPCR
siRNA-Specific Assays
- psiCHECK2 luciferase reporter assay
- Cell line and primary cell transfection analyzed by qPCR
- Primary cell uptake tracking via qPCR
- Ago2 loading assay for RISC incorporation
Off-Target Effect Assessment
Detailing a multi-faceted approach to evaluating off-target effects of siRNA therapeutics, encompassing both hybridization-dependent and independent mechanisms of cellular response and toxicity.
Hybridization-Dependent Assays
- psiCHECK2 seed sequence analysis
- Cytotoxicity in target knockout cell lines (CTG assay)
- Transcriptomic profiling via RNA-seq and microarray
Hybridization-Independent Assays
- TLR3/TLR7/TLR8 cytokine release assays (PBMCs: ELISA/Luminex)
- Reporter assays using HEK-Blue TLR-expressing cells
- Complement activation studies
- Toxicity assays in primary hepatocyte and kidney cell models
More Proven Results
Case Study: iPSC-Derived Neuronal Models for ASO Evaluation
Objective
To assess the efficacy of ASOs targeting UBE3A using iPSC-derived cortical neurons.
Assays
- ASO Treatment: Neurons were dosed on day 14 and monitored over a 9-day period.
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- Gene Expression Analysis: Upregulation of UBE3A; Downregulation of UBE3A-ATS. Both confirmed via qPCR assays.
Key Results
The results demonstrated the efficacy of ASO in modulating target genes in neuronal models, highlighting its potential for neurotherapeutic applications.
Empower Your RNAi Research Today
Partner with Medicilon to access innovative siRNA solutions backed by scientific rigor and a proven track record.
Whether you’re focused on therapeutic development or fundamental research, Medicilon’s siRNA platform delivers results you can trust.
