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Scientific Drivers
Viral vectors
Technology in Development
Issues
rAAV 2, 4, 5
Safety
Physical stability, small size; Transduction efficiency;
Chromosome integration
Efficiency
Manufacturing
Helper virus contamination, immune response
eliminated
Long-term transgene expression
Linear dose-response
Initial Phase 1 study results
Scientific Drivers
Porous biomaterial scaffolds - natural polymers, e.g. collagen
Technology in Development
Issues
Recombinant collagen
Safety
Efficiency
Manufacturing
Formulation
Scientific Drivers
Potential synergies between DNA vectors and porous biomaterial scaffolds
Week
s
in-life
2
Technology in Development
Multiple genes
6
Printing
Scaffold composites
12
MEMS
18
100.0-mg pMat-1
Key Challenge
Safety
Interaction between gene-based
therapy and tissue at delivery site
Vector persistence and bioavailability
Interaction between gene-based
therapy and immune system
Local and systemic PK/PD of vectorencoded protein
Key Challenge
Regulated transgene expression
Low baseline
expression
High induction ratio
Positive control by
small molecule drug
Control Parameters
DNA vector and porous biomaterial scaffold
Variation associated with site and extent of tissue
injury
Rate constants for cell proliferation-migration within
biomaterial scaffold
Gene transfer efficiency
Rate constants for therapeutic protein production
Pharmacokinetics and pharmacodynamics of
vector-encoded protein
Safety factors that influence gene transfer
efficiency
Transgene silencing