Principal Scientist, Shuttled Oligonucleotide Therapeutics

Manifold Bio is a dynamic biotech company building a pipeline of  targeted biologics using a novel in vivo-centric discovery approach. Our drug discovery engine is differentiated by massively parallel screening in vivo from the beginning of our discovery process. This unique platform is powered by a proprietary protein barcoding technology that allows multiplexed protein quantitation at unprecedented scale and sensitivity. We combine this and other high-throughput protein engineering approaches with computational design to create antibody-like drugs and other biologics. Our world-class team of protein engineers, biologists, and computational scientists are working together to aim the platform at therapeutic opportunities where precise targeting is the key to overcoming clinical challenges.

Position

Manifold Bio is seeking an experienced Principal Scientist to lead our shuttled oligonucleotide therapeutics programs. In this role, you will serve as a dedicated scientific leader for our oligo programs, accelerating progress on key milestones while leveraging our shuttle technology for targeting peripherally administered oligonucleotide therapeutics to specific tissues and cells. You will define the strategy for expanding our oligo capabilities and organize cross-functional teams and explore external collaborations to design novel ASOs, siRNAs, and linkers, building an efficient screening and production system that leverages our ability to do multiplexed screening in vivo. As a scientific leader, you will bring strong expertise in oligo medicines to partner conversations and accelerate the discovery of oligo therapeutics by establishing efficient techniques and assays.

Responsibilities

• Define strategy and lead  discovery and development of shuttled-oligonucleotide based therapeutics
• Combine hands-on execution at the bench, planning, and coordination among internal and external teams to rapidly advance programs
• Provide subject matter expertise to cross-functional drug discovery project teams, collaborating closely with protein engineers, in vitro biologists, bioconjugation scientists, and in vivo biologists to discover and progress shuttled oligo-based therapeutics
• Build an oligo screening and production system that supports the efficient discovery and optimization of  novel ASOs, siRNAs, and linkers
• Build and execute techniques and assays that accelerate oligo therapeutic discovery
• Select and manage external vendors necessary to support oligo discovery and development efforts
• Provide scientific leadership for internal and partnered oligo drug development programs
• Provide expert scientific and strategic input into the design of proof-of-concept studies demonstrating successful CNS target knockdown using shuttled oligos
• Clearly communicate scientific progress and challenges to team members, leadership, and collaborators
• Closely track advances in the field and provide strategic direction for continued development and expansion of Manifold’s shuttled oligo discovery efforts.

Required Qualifications

• PhD in a relevant field (nucleic acid chemistry/biology, biochemistry, biophysics, molecular biology, or related discipline)
• Minimum of 6 years post-PhD experience, including experience in biotech/pharma drug discovery and development
• Strong background in oligonucleotide chemistry, including backbone and base modifications to improve potency and other desired properties
• Experience building and/or optimizing platforms for oligo design, synthesis, and screening
• Hands-on experience with multiple oligonucleotide modalities (ASOs, siRNAs, aptamers, mRNA) and different backbone chemistries/modifications
• Experience progressing oligonucleotide therapies through nonclinical/early clinical development
• Knowledge of proven and emerging technologies for delivering oligo medicines to cellular targets (LNPs, passive or active targeting moieties, etc.)
• Understanding of DMPK, toxicology, and developability considerations specific to oligos
• Excellent written and verbal communication skills

Preferred Qualifications

• Experience designing linkers and/or active delivery mechanisms for tissue-targeted nucleotide therapeutics
• Experience in the design and interpretation of cell-based or in vivo measurement of oligonucleotide efficacy
• Experience with in vivo knockdown studies
• Demonstrated leadership of small scientific teams
• Experience leading matrixed project teams through discovery and/or development efforts
• Demonstrated ability to mentor junior scientists
• Strong presentation skills and design sensibility

This Role Might Be Perfect For You If:

You are curious, and passionate about science and drug discovery and want to work with a fast-moving team that values scientific boldness and innovation. This role requires deep technical expertise combined with a willingness to work thoughtfully and quickly to solve scientific challenges in a collaborative manner. You value an experimental approach and generating high-quality data to empower rapid, data-driven decision-making, with a commitment to meet or beat critical deadlines. You should be a team player who is also proactive and resourceful.

If you’re excited to use unique protein technologies to shape an innovative drug development strategy, build meaningful industry partnerships, and contribute directly to our mission of advancing breakthrough treatments, please apply!

We value different experiences and ways of thinking and believe the most talented teams are built by bringing together people of diverse cultures, genders, and backgrounds.