Call for Proposals

1.

Current design processes for siRNA and/or ASO drug candidates are not sufficiently holistic to predict downstream effects.

• Accelerate drug development through smart design
• Improve drug profile early in development
• Tighten iterative loop between design and testing

• A disease-agnostic algorithm (or a set of algorithms) for ASO and/or siRNA that demonstrates the following:
  • Hit rate of >20% with picomolar IC₅₀ (potency), acceptable efficacy, stability, specificity (off-target value), and cytotoxicity profile with validated in vitro assays
  • New and broadly applicable combinations of known chemical modifications, leading to better performance than benchmark sequences (approved drugs or clinical trial candidates), measured using in vitro and in vivo assays
• An integrated, preferably automated system of robust, validated in vitro assays to evaluate at least 96 siRNA and/or ASO drug candidates simultaneously for characteristics including but limited to the following:
  • Efficacy/potency
  • Stability
  • Specificity (off-target value)
  • Cytotoxicity
  • Mechanistic functions (e.g. RNase H cleavage, Ago2 loading, ribosomal loading)
• Use of electronic laboratory notebooks to digitise and centralise management of experimental data, to facilitate downstream drug development

Optional

• Collaboration with data partners (e.g. industry) to test and validate new algorithm(s)
• Use of artificial intelligence and/or machine learning

1.

Limited access to bespoke chemistries and modifications impedes synthesis of hit compound libraries for siRNA/ASO drug development.

• Support hit compound synthesis
• Develop novel chemical modifications for siRNA and/or ASO drugs

• A robust, high-throughput workflow for oligonucleotide synthesis that achieves the following:
  • Ability to synthesise siRNA and ASO with a mixture of standard chemical modifications
  • Quality control demonstrating >80% purity and other standard quality attributes required for hit screening
  • Turnaround time of <2 weeks to generate a library of at least 96 distinct candidates each for siRNA and ASO
• At least 1 novel chemical modification to demonstrate at least one of the following improvements, using relevant in vitro and in vivo functional assays:
  • Increase potency
  • Extend duration of drug effect
  • Improve release into the cytosol
  • Reduce toxicity
• Use of electronic laboratory notebooks to digitise and centralise management of experimental data, to facilitate downstream drug development

Optional

• Collaboration with knowledge partners (e.g. industry) to test new chemistries
• Use of automation to increase throughput, streamline workflows, and/or reduce costs

1.

Current designs for mRNA drug candidates are not sufficiently effective.

• Accelerate drug development through smart design
• Improve drug profile early in development

• A disease-agnostic algorithm (or a set of algorithms) to design linear and/or non-linear mRNA drugs, that achieves the following:
  • >6-fold increase of in vitro protein expression compared to benchmark sequences (i.e. approved drugs or clinical trial candidates)
  • >3-fold increase of in vivo expression, along with similar efficacy, durability, and safety compared to benchmark sequences, via intramuscular administration and separately via intravenous administration, using established delivery methods and validated assays
• Use of electronic laboratory notebooks to digitise and centralise management of experimental data, to facilitate downstream drug development

Optional

• Collaboration with data partners (e.g. industry) to test and validate new algorithm(s)
• Use of artificial intelligence and/or machine learning

1.

Current development of safe and effective carriers to encapsulate nucleic acid drugs for various clinical applications is not sufficiently efficient.

• Accelerate development of safe and effective carriers
• Diversify raw materials for nucleic acid encapsulation

• An integrated system to develop carriers for encapsulating nucleic acids, that features the following:
  • Ability to investigate a broad range of lipids, polymers, and other raw materials for formulating carriers;
  • Ability to simultaneously evaluate a series of standard quality attributes minimally including particle size, polydispersity, translation efficiency, and cytotoxicity in vitro 
  • At least two viable applications based on the route of administration, for example:
    • One novel formulation for intramuscular administration to achieve in vivo efficacy, safety and stability comparable to or better than a benchmark drug (e.g. COVID-19 vaccine)
    • One viable formulation for intravitreal administration, transdermal administration, or other routes of administration, achieving acceptable in vivo efficacy, safety and stability using a reference standard
• Use of electronic laboratory notebooks to digitise and centralise management of experimental data, to facilitate downstream drug development

Optional

• Collaboration with suppliers (e.g. industry) to increase access to raw materials
• Use of automation to increase throughput, streamline workflows, and/or reduce costs
• Use of artificial intelligence and/or machine learning