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Senior Scientist - Upstream Process Development

4D Molecular Therapeutics
Emeryville, California
Start date
Mar 19, 2024

Job Details

Attention recruitment agencies: All agency inquiries are vetted through 4DMT’s internal Talent Acquisition team. No unsolicited resumes will be accepted. Agencies must be expressly engaged by the 4DMT Talent Acquisition team on any requisition. Agencies reaching out directly to hiring managers will not be tolerated and doing so may impact your ability to work with 4DMT in the future.


4DMT is a clinical-stage biotherapeutics company harnessing the power of directed evolution for targeted genetic medicines. We seek to unlock the full potential of gene therapy using our platform, Therapeutic Vector Evolution (TVE), which combines the power of directed evolution with our approximately one billion synthetic AAV capsid-derived sequences to invent evolved vectors for use in our products. We believe key features of our targeted and evolved vectors will help us create targeted product candidates with improved therapeutic profiles. These profiles will allow us to treat a broad range of large market diseases, unlike most current genetic medicines that generally focus on rare or small market diseases.  

We have built a deep portfolio of AVV-based gene therapy product candidates, with five product candidates in clinical trials: 4D-150 for the treatment of wet age-related macular degeneration (wet AMD) and diabetic macular edema (DME), 4D-710 for the treatment of cystic fibrosis lung disease, 4D-310 for the treatment of Fabry disease cardiomyopathy, 4D-125 for the treatment of X-linked retinitis pigmentosa (XLRP), and 4D-110 for the treatment of choroideremia. In addition, we have two product candidates in preclinical studies: 4D-175 for geographic atrophy (GA) and 4D-725 for alpha-1 antitrypsin deficiency.

To-date, we have demonstrated clinical proof-of-concept for three evolved vectors in three therapeutic areas and routes of administration with five products and patient populations. We believe this validates the power of our directed evolution platform for discovering superior vectors compared to wildtype viral vectors. We have built a robust and efficient product engine with 6 open Investigational New Drug Applications (INDs) in the U.S., 1 IND in Taiwan, and 1 Clinical Trial Approval (CTA) in Australia. We believe we are positioned to create, develop, manufacture and, if approved, effectively commercialize targeted genetic medicines that could transform the lives of patients suffering from debilitating diseases.

In addition to TVE, our technology includes a robust AAV manufacturing platform and onsite manufacturing facility that allows us to rapidly produce and test research grade material and scale up to GMP clinical material. This internal capability and close collaboration between our R&D and Manufacturing teams has greatly accelerated the pace of discovery at 4DMT.

Company Differentiators: 

•    Fully integrated clinical-phase company with internal manufacturing
•    Demonstrated ability to move rapidly from idea to IND
•    Five candidate products in the clinic and two declared pre-clinical programs
•    Robust technology and IP foundation, including our TVE and manufacturing platforms
•    Initial product safety and efficacy data substantiates the value of our platforms
•    Opportunities to expand to other indications and modalities within genetic medicine


We seek a talented and passionate Senior Scientist, Upstream Process Development to join our leading-edge Upstream Process Development team to support development and commercialization of AAV gene therapy products. The candidate will lead our late-phase process development efforts, including internal process characterization and external PPQ at a CMO. This is a cross-functional role, working to ensure robustness of our late-stage clinical programs and to accelerate the commercialization of our gene therapy programs. This person will report to the head of Upstream Process Development and is responsible for implementing Quality by Design (QbD) principles towards 4DMT’s maturing clinical assets. They will also interact closely with the following teams: Downstream Process Development, Analytical Development, Supply Chain and Upstream Manufacturing. The candidate should be passionate about science, possess excellent collaboration and communication skills, and enjoy the challenges associated with complex problem solving. 


Experimental Design and Execution: 60% of TIME 

  • Implement and provide guidance on integrating QbD principles towards late stage clinical assets with emphasis on the upstream process (cell thaw through clarification) 
  • Design and execute studies that evaluate process robustness and product consistency, focusing on HEK293 cellular expansion, transient transfection and AAV production 
  • Trend development and manufacturing data to inform process consistency and improve/qualify scale down models  
  • Author study designs, process descriptions, standard operating procedures and author regulatory documents supporting IND and BLA submissions 
  • Assist manufacturing technical support, including process trouble-shooting, root cause analysis and investigation on process and/or quality discrepancies and deviations during GMP productions, change controls and CAPAs 

 Cross-functional & communication : 40% of time 

  • Lead and coordinate pre-PPQ and PPQ activities at a CMO, with an emphasis on upstream operations (cell thaw through concentration by tangential flow filtration) 
  • Mentor colleagues within upstream process development with opportunity to manage a small group in the near future  
  • Lead technical investigations for internal/external manufacturing that include troubleshooting, root cause analysis and/or deviations  
  • Collaborate with process & analytical teams to screen and evaluate drug candidates across a range of indications 
  • Maintain strong working relationships with external collaborators, vendors and internal/external manufacturing groups 
  • Other duties as assigned, nothing in this job description restricts management’s right to assign or reassign duties and responsibilities to this job at any time 



  • Bachelor’s/Master’s degree in an engineering or life science discipline with 12+/10+ years of experience  
  • PhD degree in an engineering discipline with 4+ years of relevant experience 


  • 4+ years with analysis and modeling of preclinical and clinical manufacturing data  
  • 4+ years with product life cycle and QbD-based risk management supporting clinical through commercial drug development 
  • 2+ years with mammalian cell culture and/or gene therapy 


  • Strong problem-solving, analytical skills and creativity 
  • Experience in both leading and supporting late clinical stage initiatives  
  • Working knowledge of GMP and manufacturing  
  • Experience with statistical analysis and numerical methods suitable for experimental design 
  • Strong written and oral communication skills with experience presenting scientific information 
  • Excellent time management organizational skills, with ability to handle multiple tasks simultaneously in a high-growth, fast-paced environment 


Base Salary Compensation Range:

Bay Area Range: $163,000/yr - $189,000

Please note, the base salary compensation range and actual salary offered to the final candidate depends on various factors: candidate’s geographical location, relevant work experience, skills, and years of experience.


Base Salary Compensation Range:

Bay Area Range: $163,000/yr - $189,000

Please note, the base salary compensation range and actual salary offered to the final candidate depends on various factors: candidate’s geographical location, relevant work experience, skills, and years of experience.





4DMT provides equal employment opportunities to all employees and applicants for employment without regard to race, color, religion, gender, sexual orientation, national origin, age, disability, genetic information, marital status, status as a covered veteran, and any other category protected under applicable federal, state, provincial and local laws.   Equal Opportunity Employer/Protected Veterans/Individuals with Disabilities


4DMT is a gene therapy company with a transformative discovery platform --Therapeutic Vector Evolution --that enables our “disease first” approach to product discovery and development, thereby allowing us to customize our AAV vectors to target specific tissue types associated with the underlying disease.

At 4DMT we are creating and developing optimized “biopharmaceutical grade” AAV vectors that will allow us uniquely to unlock the full potential of gene therapy. Our customized and proprietary AAV vectors are each designed, according to a 4DMT Target Vector Profile, to deliver genes to specific cells and tissues in the body to eradicate both rare and large market diseases.

While AAV gene therapy pioneers are making great strides with the first wave of products, hurdles still exist with the use of conventional vectors. The most commonly used AAV capsids (e.g., AAV2, 5, 8 and 9) were identified either 1) as contaminants in lab stocks of adenovirus, or 2) through monkey tissue processing. Therefore, these conventional vectors are not targeted specifically to any tissue in the body. This can lead to inefficient and non-specific delivery, thus requiring extremely high doses and potentially resulting in toxicities (including inflammation), high manufacturing burdens and suboptimal efficacy. In addition, suboptimal routes of delivery can be required for delivery to the right tissues (e.g., subretinal delivery to the retina). Finally, pre-existing neutralizing antibodies in many patients can limit efficacy, clinical trial enrollment and market sizes. 4DMT Innovation empowers us to create new and improved next generation AAV capsids to allow targeted delivery of our products by the optimal clinical route of administration.

At 4DMT we use our robust discovery platform, termed “Therapeutic Vector Evolution,” to create customized and proprietary gene delivery vehicles (novel AAV vectors) to deliver genes to specific tissues and cells in the body by the optimal route of administration. We use the power of evolution to create and refine these optimized vectors through genetic diversification and then natural selection in vivo.

4D Purpose Statement:  Boldly Innovating to Unlock the Full Potential of Gene Therapy for Countless Patients



  • Dare to Cure - Patients are waiting. Create big dreams for patients and take calculated risks to achieve them
  • Break Boundaries - Question the status quo and innovate beyond conventional approaches
  • Beyond Yourself - It's about patients, their families, our team, our families. We strengthen each other.
  • Prepare and Execute Relentlessly - Start with the end in mind, over-prepare and make contingency plans to your contingency plans

We invite all of you who share our passion and vision in creating the ultimate gene therapy products to cure genetic and rare diseases in children and adults. We seek the best people in the industry who identify with our mission and innovative results-driven approach. We offer an inspiring and collaborative environment that encourages individual contributions, recognizes performance in multiple ways, offers generous benefits and provides challenging opportunities for career development. 

Company info
5858 Horton St. Suite 455
United States

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