Adenoviral vectors: What is the typical maximum foreign DNA insert size that first-generation adenovirus vectors can accommodate?

Introduction / Context:
Adenovirus-based vectors are widely used in gene delivery because they efficiently transduce many cell types. Their packaging capacity is limited by the viral capsid and genome requirements. This question targets recall of the commonly accepted insert capacity for first-generation designs.

Given Data / Assumptions:

• We are considering first-generation adenoviral vectors with standard deletions (e.g., E1/E3).
• Insert size refers to foreign DNA beyond the essential viral sequences that must remain.

Concept / Approach:
First-generation adenoviral vectors typically allow insertion of approximately 6–8 kilobases of foreign DNA while keeping the total genome length within the capsid packaging constraints. Although “gutless” or helper-dependent adenoviral systems can package larger payloads (approaching 30–36 kb), those are specialized constructs and not implied in standard, first-generation vectors.

Step-by-Step Solution:

Verification / Alternative check:
Gene therapy manuals and vector datasheets frequently cite a working capacity near 7–8 kb for first-generation adenovirus; more than this risks inefficient packaging or instability.

Why Other Options Are Wrong:

• 4–6 kb: too conservative for standard E1/E3-deleted vectors.
• 10–12 kb or 20 kb: exceed first-generation norms.
• ≥30 kb: applies to helper-dependent systems, not the basic format implied by the question.

Common Pitfalls:
Confusing capacities of different adenoviral generations; mixing adenovirus with AAV capacities (AAV ~4.7 kb).

Final Answer:
6–8 kb