Our Customized srRNA Platform

a platform like no other

The Replicate srRNA platform starts with virally derived RNA that we modify so that it is no longer able to produce virus. We do this by removing the genes responsible for the viral shell, leaving intact the genes that are responsible for duplication of the viral RNA: this is the srRNA vector. The srRNA vector contains both instructions for making a specific protein and a “copying machine” that reproduces those instructions over and over. When the srRNA is injected into cells of the body, the cells continue to receive the instructions and produce the protein.

Since the srRNA vector lacks the viral shell genes, it cannot spread to other cells as a virus would, nor does it integrate into the genome.

Because the srRNA vector replicates itself hundreds of thousands of times, materials required for dosing can be reduced by several orders of magnitude compared to mRNA or other RNA therapeutics.

1.

rna enters the cell

2.

rna replicates and mimics virus

3.

rna translated by body to produce proteins

Each Replicate srRNA vector is tailored to meet the unique requirements of its encoded therapeutic protein. Replicate chooses not to deploy the standard “one size fits all” approach to vector design and instead embraces the diversity present in nature. Because no one vector can do the job for all, Replicate screens and generates panels of proprietary vectors and further optimizes through synthetic biology to build versatile srRNAs.

Replicate Harnesses Synthetic Biology to Develop and Advance Improved Vectors

ONE SIZE DOES NOT FIT ALL FOR DRUG DEVELOPMENT

Unpredictable interplay between:

  • Encoded gene
  • Host cell
  • Virally delivered synthetic vector
  • Delivery formulation

TOOLBOX OF SYNTHETIC VECTORS

  • Derived from new viral species or subtypes, allowing selection of best vector for encoded gene

Therapeutic Applications

Replicate srRNAs are designed to flip the switch on the immune system to either “active” or “stealth” mode, depending on the therapeutic need.

One type of Replicate srRNA alerts the immune system to drive a strong response to fight drug-resistant mutations in cancer. It works like this: Once the srRNA molecule enters a cell, it creates thousands of copies of itself and uses the cell’s own machinery to manufacture abundant amounts of proteins responsible for drug resistance. Because this replication process mimics a viral infection, it educates the immune system to recognize and attack the tumor cells that express these drug-resistance-causing proteins.

Another type of Replicate srRNA is engineered to cloak itself from the immune system and triggers the manufacture of protein that evades an immune attack. This type of srRNA is designed to treat autoimmune diseases, in which higher amounts of a therapeutic protein may be needed for a beneficial effect. Such quantities of therapeutic protein could not be administered with most vectors without triggering an adverse immune reaction.

The Replicate srRNA platform lends itself also to potential applications in infectious diseases and other disease areas.

Administration of Replicate srRNAs

Some Replicate srRNA therapeutics are designed to spur the production of proteins by cells in ways that alert the immune system to activate and drive a strong response to fight cancer or infection. Other Replicate srRNA therapeutics are engineered to enable cells to manufacture proteins that are cloaked to the immune system and evade immune attack; this approach is applicable to auto-immune diseases in which high amounts of a therapeutic protein may be needed for a beneficial effect.

A Versatile Platform with Diverse Applications

Self-replicating RNAs can express many types of therapeutic molecules

Antibodies

Cytokines

Pathogen Proteins

Protein (ant)agonists

enzymes

Our Capabilities

Replicate scientists have significant experience in srRNA product formulation, with particular expertise in assessing the independent effects of vector, payload configuration, and formulation (such as lipid nanoparticle compositions or polymers) on expression.

Four pillars of activity for srRNA drug development

1. Protein Insert

Proteins with designs to match our vectors, and proprietary processes to combine multiple genes in a single vector

2. Vector

Diverse vectors, drawn from nature and functionally enhanced with synthetic biology and our molecular design principles

3. Delivery

Varied delivery technologies to customize each drug product for any indication, for maximum therapeutic effect

4. Manufacturing

Team with extensive experience pioneering srRNA manufacturing solutions

Replicate is one of the first organizations to show that these four areas are fully independent variables—a learning we have applied in our platform’s customized approach.