Regulatory Science Symposium: “Innovations in Regenerative Medicine Products” Session 6: Target Identification for Gene Therapy + Symposium Wrap-up


  1. Presentation outline:
    1. Gene therapy
    2. Schematics
    3. Target Product Profile (TPP)
    4. Huntington's Disease
    5. Illustrative Programs
    6. Takeaways
  2. Gene therapy:
    1. Gene therapy definition
    2. Can work by several mechanisms
    3. Broad applicability
  3. Why do we need another “therapeutic modality”? (comparison of drugs and gene therapy)
    1. Small molecules:
      1. Pros: Cheap and orally bioavailable
      2. Cons: Limited target traceability and chronic administration
    2. Gene therapy:
      1. Pros: All genetic targets are accessible with “one and done” mechanism
      2. Cons: Limited distribution, costly, relatively new field - limited safety data
    3. It works! There are FDA-approved therapies.
  4. Schematic: Elements of gene therapy “drug”
    1. Payload (genetic material to be delivered – DNA-based/RNA-based)
    2. Flanking sequences (Promoter, Viral LTRs, caps, and non-natural nucleotides)
    3. Vector: Gene Carrier
    4. Viral (sero) type: Virus which doesn’t introduce a disease
  5. Target Product Profile: Specification for Safety and Efficacy
    1. Target validation: The desired target
    2. Desired pharmacology: The desired gene product
    3. Biodistribution: Which organ(s)/tissue(s), which cell type(s)
    4. Root of administration: Ex-vivo(mostly), peripheral administration, central administration
    5. Safety: Risk-benefit of “irreversible” treatment - when to treat prevention/too early versus reversal/too late
  6. Huntington’s Disease (background,
    1. Discovered by George Huntington in 1872
      1. Describes movement disorder and chorea
      2. Hereditary disease
    2. Autosomal Dominant
      1. Males and females have the same chance, no “recessive carries”, children have 50:50 chances of having it.
    3. Monogenic disease with 100% penetrance
    4. Relatively rare disease with a ratio of 1:10,000
    5. The full sequence of the gene was discovered in 1993 for Huntington's disease
    6. Causes
    7. Enables Genetic Testing (diagnostics):
      1. Predict who is going to get the gene and when
      2. Enables family planning, pre-implantation genetic diagnostics
    8. Can make animal models of HD
    9. Gene Therapy (modulation of a gene)
    10. During Transcription:
      1. AAV-ZFP
      2. CRISPR-Cas 9
      3. Small Molecule Transcription blocker
  7. During Translation:
    1. AAV-miRNA
    2. ASO
    3. siRNAs
    4. Small molecule translation blocker
    5. Degradation enhancers
  8. Development of pharmacodynamic biomarkers
    1. Many diseases like Huntington's disease are developing in human beings
    2. Therefore, a biomarker was developed to identify IF there is any kind of defect in the human gene or not.
    3. CHDI in collaboration with others used cerebrospinal fluid from the Huntington patients to check their Huntington levels in their body.
  9. Discussion on Huntington's Disease gene therapy profile
  10. Illustrative Programs:
    1. Example 1: Takeda’s TAK-686
    2. Example 2: uniQure’s AMT-130
    3. Example 3: Voyager
  11. Takeaways
    1. Despite initial difficulties, gene therapy remains an important modality
    2. Hundreds of other diseases are a candidate for gene therapy
    3. Significant advances in viral capsids promise improved safety profiles, facile routes of delivery, precise special and temporal targeting
    4. Large (and evolving) array of payloads
    5. Challenges remain
  12. Questions
  13. Symposium Wrap-up
    1. Symposium resource: “Innovations in Regenerative Medicine Products and Types of Regenerative Medicine Therapies”
    2. Can be found in the electronic binder
  14. Complete program evaluation survey to receive certificate of completion
  15. Wrap-up discussion
  16. Thank you!

Accompanying text created by Roxy Terteryan, RKS Project Administrator, SC CTSI (


Eunjoo Pacifici, PharmD, PhD
Chair and Associate Professor of Regulatory and Quality Sciences Associate Director, D. K. Kim International Center for Regulatory Science

NIH Funding Acknowledgment: Important - All publications resulting from the utilization of SC CTSI resources are required to credit the SC CTSI grant by including the NIH funding acknowledgment and must comply with the NIH Public Access Policy.