Architecture Portfolio
Candidate Delivery Architectures
Compare plausible architecture options and surface why each fits, where each fails, and what validation should happen next.
Engineered AAV systemic CNS delivery
Summary
Novel capsid family optimized for BBB crossing with liver detargeting motifs.
Why it fits
Matches need for broad CNS coverage with durable expression and low procedural burden.
Main benefit
High upside for scalable CNS exposure from IV route.
Main limitation
Immune escape and translational variance remain major uncertainties.
Key engineering lever
Capsid loop engineering + miRNA liver detargeting module
Recommended next validation
NHP CNS:liver exposure ratio and neutralization profile.
AAV with liver-detargeting priority
Summary
Prioritize off-target suppression and hepatic burden reduction over max potency.
Why it fits
Useful when safety margin is narrow and liver tox is primary gating risk.
Main benefit
Potentially better safety at equivalent systemic dose.
Main limitation
May underperform on deep brain cell coverage.
Key engineering lever
Detargeting motifs + promoter gating
Recommended next validation
Rodent and NHP liver enzyme + brain efficacy curve mapping.
Dual-AAV split-payload strategy
Summary
Split oversized constructs into co-delivered vectors with recombination logic.
Why it fits
Applicable when payload complexity exceeds single-capsid packaging limits.
Main benefit
Extends AAV to larger therapeutic designs.
Main limitation
Co-transduction inefficiency and manufacturing complexity.
Key engineering lever
Payload architecture optimization + stoichiometry tuning
Recommended next validation
Cell-type matched co-expression recovery studies.
Intrathecal/local administration AAV
Summary
Route optimization to bypass systemic barriers and reduce peripheral burden.
Why it fits
Strong where localized CNS regions can drive clinical benefit.
Main benefit
Lower systemic exposure and potentially lower dose.
Main limitation
Procedural burden and uneven tissue distribution.
Key engineering lever
Route protocol + local tropism tuning
Recommended next validation
CSF gradient mapping with region-specific transduction endpoints.
LNP transient editor delivery
Summary
Non-viral editing payload with repeat dosing flexibility.
Why it fits
Alternative when AAV immunity or durability profile is misaligned.
Main benefit
Potential redosing and immune profile advantages.
Main limitation
Durability and CNS distribution may be insufficient.
Key engineering lever
Particle chemistry and targeting ligand design
Recommended next validation
Head-to-head biodistribution with AAV benchmark arm.