mRNA Platform

In silico platform for biopharma scientists to design mRNA therapeutic candidates

Context

mRNA-based therapeutics : Heralding a new class of drugs

Rather than provide a vaccine made from viral proteins, this COVID-19 vaccine is composed of synthetic viral mRNA. These molecules are injected into people and cellular protein-making machines, called ribosomes, read and translate the mRNA. It’s these proteins that then trigger an immune response.
mRNA vaccine eliciting an immune response and producing antibodies against SARS-CoV-2 protein

Success of mRNA vaccines against SARS-CoV-2 has demonstrated the great potential of mRNA based therapies. The potential of mRNA sequence to produce specific proteins using cells’ own translation machinery without causing any permanent alteration to the DNA sequence makes it an important modality.

Key challenges in mRNA design include:

  • Selecting the optimal coding sequence of mRNA from a formidably large search space
  • Multidimensionality of the problem space leading to increased expenses, manpower, and computation time
  • Ensuring ex vivo and in vivo stability as well as translation efficiency
  • Lack of customizable and scalable pipelines for complete mRNA characterisation and design

The platform consists of an integrated end-to-end pipeline for complete mRNA design. It offers researchers the ability to tailor an entire mRNA through:

  • Target Protein Selection
  • mRNA Coding Sequence Optimization
  • Compatible non-coding Parts Design

The solution is deployed on a computational platform for high throughput screening and cloud-based Kubernetes environment with schedulers such as SLURM for auto-scaling and workload management.

Our Solution

An in silico platform for designing effective mRNA therapeutic candidates leveraging advanced computational algorithms and scalable infrastructure

mRNA pipeline consisting of key steps - Select target protein, Design CDS, Design 5’-UTR, Design 3’-UTR, Design poly(A) tail, and Build the complete mRNA
mRNA pipeline deployed on a scalable cloud infrastructure

Key steps of the mRNA pipeline include:

Identify the target protein sequence by analyzing its physicochemical properties such as stability, solubility, transportability, etc.
01
02
Optimize the coding region of the mRNA sequence (CDS)
Characterize the stability & translation efficiency of the optimized CDS and its chance of getting hydrolyzed
03
04

Check the presence of Kozak consensus sequence in the designed mRNA

Visually analyze the the secondary structure of Translation Initiation Site (TIS) and the 3′-UTR
05
06
Build the poly(A) tail
Analyze the final complete mRNA sequence for pharmaco kinetic properties
07
Highlights

Key components & strengths

An end-to-end solution for mRNA sequence design

A platform to build the complete mRNA sequences including coding and non-coding parts optimized for best therapeutic outcomes

Efficient algorithms for mRNA optimization

Leveraging search/filter algorithms to optimize folding stability and translation efficiency for arriving at an optimized mRNA sequence design in short time

Customizable solution components

Modules leverage open-source packages where appropriate and are designed for easier customization

Cloud-based and on-demand computational infrastructure

HPC clusters, cloud-based Kubernetes environment for auto-scaling, and schedulers such as SLURM for workload management, resulting in high throughput
Outcomes

Accelerate mRNA-based drug discovery and development

Reduced search space

Of possible mRNA sequences by simultaneously optimizing parameters such as half-life, translation efficiency, etc.

Reduced cycle time

To filter and find a better target protein through comprehensive characterization and evaluation of ADMET properties

Faster selection

Of compatible non-coding sequence for a given coding sequence of the mRNA to ensure better protein synthesis

Scalable computation

With infrastructure as a code approach and on-demand auto-scaling techniques

Discover our offerings across the biopharma value chain

Learn more about our mRNA Platform