A Novel Class of Functional RNA Molecules

GenScript proudly offers custom circular RNA (circRNA) synthesis via our proprietary circRNA IVT manufacturing service.

circRNA is a single-stranded RNA in which the 5’ and 3’ ends join to form a covalently closed loop. The circular structure confers multiple functional benefits, including improved stability and longer expression duration.

Custom circRNA synthesis is available now for 100bp – 4 Kb insert sequences with delivery in only 3 weeks.

Benefits of circRNA

Proprietary circRNA vector and purification method, leading to high circularization efficiency and purity

Improved stability & increased and longer protein expression duration vs linear mRNA

Cell-specific IRES options optimized for different applications

Comparison of different IVT RNA payload formats

Linear mRNA Self-Amplifying RNA Circular RNA
Structure Linear; Open 5’ and 3’ end
mRNA exonuclease degradation
Linear; Open 5’ and 3’ end
mRNA exonuclease degradation
Close loop; No free 5’ 3’ end
Eliminating mRNA exonuclease degradation
Ribosome recruiting 5’ Cap:
Initiates translation & stabilizes mRNA
5’ Cap:
Initiates translation & stabilizes mRNA
Internal Ribosome Entry Site (IRES) :
Initiates translation
ORF
  • Codon optimization for translation yield
  • Modified nucleosides, eg. M1Ψ
  • Insert < 20 kb
  • Codon optimization for translation yield
  • Modified nucleosides, eg. M5C
  • Insert < 6 kb
  • Codon optimization for translation yield
  • Insert < 4 kb
UTR Regulatory elements in the 5’ and 3’-UTR stabilize mRNA and increase translation initiation Replicon for further self-replication of the mRNA Include IRES + PIE + other elements
PolyA tail Stabilizes RNA molecule & Prevents degradation Stabilizes RNA molecule & Prevents degradation Not required
Protein Expression +++ Strong +++++ Strongest ++++ Stronger
Expression half-life +++ Shorter +++++ Longest ++++ Longer
Immunogenicity ++++ Low ++ High +++ Medium
Dosage requirement ++ High +++++ Lowest +++ Medium
Novelty +++ Traditional ++++ Novel +++++ Novel

Service

Codon/UTR
Optimization
  • Codon optimization for protein expression offered every day for every gene
  • Codon optimization with >200 factors screened (patent)
Gene
Synthesis
  • 100 bp – 4 kb gene inserts
  • TAT as fast as 6 BDs to 14 BDs
Cloning/Plasmid
Synthesis
  • Ready to use linearized plasmid DNA for IVT
circRNA
Synthesis
  • Proprietary RNA circularization process
  • QC analysis
Lipid Nanoparticles
Delivery
  • Generic ionizable lipid formulation
  • Load 1-30mg, up to 10kb mRNA

GenScript circRNA offers the flexibility to meet your project needs

Popular off-the-shelf circRNA catalogs available now!

Try our catalog mRNA expressing eGFP or F-Luciferase, delivered in just 5 days! Learn More >>

Workflow

Send Us Your ORF or IRES

We will design your circRNA expression vector with T7 promoter, PIE, IRES and ORF

Gene Synthesis to Plasmid Prep

Our integrated workflow will take care of all the prerequisites to produce your circRNA

RUO Grade IVT Production

µg to mg customized RUO circRNA service with advanced purification (RP-HPLC) and QC options

Quality Control and Specification

QC Item Test Method Specification RUO
Default
RUO
Upgrade
Identification Appearance Visual Inspect Clear and free of foreign particles
RNA Length Agarose Gel Electrophoresis Expected size band detected​
Identification RNaseR degradation test​ Not be degraded by RNaseR
RNA Content​ UV Absorbance​ Target ± 5%​
PH pH meter Target ± 0.5
Buffer Specification Client Spec N/A
Purity A 260/280 Ratio UV Spec 1.70 ~ 2.30
Purity by HPLC HPLC ≥80 %​
Impurity Total protein residue Nano Orange Assay ≤ 1%
Plasmid DNA Residue qPCR ≤ 0.1%​
Safety Endotoxin Semiquantitative < 10EU/mg
Endotoxin Quantitative < 10EU/mg
Bioburden Sdirect Inoculation No Growth after
48 hrs

Case Studies

Resources

Circular RNA Case Study Report
Circular RNA Case Study Report

Circular RNA introduction, GenScript offering details, and case studies showing increased stability, prolonged expression, and lower immunogenicity compared to linear IVT mRNA.

Free Download
Circular RNA Beginner’s Guide_Infographic
Circular RNA Beginner’s Guide_Infographic

Learn about key structural components of circRNA, the process by which circRNA is translated into protein, and more.

Free Download

FAQs

Additional mRNA Offerings

Get in Touch
with GenScript Custom Circular
RNA Synthesis

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