Head of RNAi Discovery & Lead Optimization

Pliant Therapeutics; South San Francisco (CA); Hybrid; USD 290,000 - 320,000; Full time

Benefits offered by this job

Equity

Annual bonus

Job summary

Pliant Therapeutics is seeking a Head of RNAi Discovery to build and lead our siRNA discovery engine. This leader will own end-to-end strategy, from bioinformatic design of libraries to chemistry optimization and in vitro screening, coordinating with biology, DMPK, CMC and program teams.

Hybrid role requiring 3 days/week in South San Francisco. The role emphasizes hands-on RNAi design, team leadership, and delivering high-quality siRNA candidates, with collaboration across functions and external

Qualifications

• PhD in molecular biology, biochemistry, chemistry, computational biology or related field; 12+ years industry experience, including 5+ years in RNAi discovery.

Responsibilities

• Define and execute the siRNA discovery strategy from target nomination through lead selection.
• Lead bioinformatic design of siRNA libraries with cross-species coverage.
• Oversee off-target analysis to prioritize sequences and refine design tools.
• Manage the team and external vendors to generate siRNA libraries and ensure timely delivery.
• Lead chemistry optimization of hits to improve potency, durability and safety.
• Build and lead the in‑vitro screening team with cell line selection and assay development.
• Coordinate with PK/PD teams for in vivo studies in mice and NHP.
• Provide knowledge to CMC and manufacturers for scalable leads.

Skills

RNAi design

Leadership

Team management

Bioinformatics

Off-target analysis

In vitro screening

In vivo PK/PD knowledge

Cross-functional collaboration

Education

PhD in molecular biology/biochemistry/chemistry/computational biology

Tools

Python

R

Job description

Pliant Therapeutics is seeking a Head of RNAi Discovery to build and lead our siRNA discovery engine. This leader will own end-to-end strategy, from bioinformatic design of libraries to chemistry optimization and in vitro screening, coordinating with biology, DMPK, CMC and program teams.

Hybrid role requiring 3 days/week in South San Francisco. The role emphasizes hands-on RNAi design, team leadership, and delivering high-quality siRNA candidates, with collaboration across functions and external