Adenovirus vs Lentivirus – Which Viral Vector Is Right For My Research?
BioInnovatise Viral Vector Team
Updated February 17, 2025
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Adenovirus and lentivirus vectors represent the odd couple of gene therapy and gene delivery—one flashy but fleeting, the other slow and steady. While adenovirus bursts onto the scene with high titers and transient expression, lentivirus prefers the long game, integrating into the genome for a permanent stay in target cells.
Scientists must weigh whether they need the adenovirus’s impressive cargo capacity and easy manufacturing or the lentivirus’s ability to stick around in dividing cells. Our viral vector team overviews the differences between adenovirus vs lentivirus in many areas.
Adenovirus vs Lentivirus Structural Differences
Capsid Structure:
- Adenovirus: Icosahedral, non-enveloped capsid (70-90 nm diameter) composed of hexon, penton base, and fiber proteins.
- Lentivirus: Spherical, enveloped virion (80-120 nm diameter) with glycoprotein spikes (often VSV-G pseudotyped).
Cargo Capacity:
- Adenovirus: ~8-36 kb depending on the generation (first-gen ~8 kb, gutless/helper-dependent ~36 kb). Read more about Adenovirus Packaging Capacity.
- Lentivirus: ~8-9 kb (limited by RNA genome size constraints). Read more about Lentivirus Packaging Size Limit.
Genomic Architecture:
- Adenovirus: Double-stranded linear DNA genome (~36 kb); transgenes typically replace E1 and/or E3 regions
- Lentivirus: Single-stranded RNA genome that’s reverse transcribed to DNA; requires LTRs, packaging signal, and elements for reverse transcription
Host Cell Integration:
- Adenovirus: Non-integrating; remains episomal in the nucleus
- Lentivirus: Integrates into host genome (though self-inactivating/SIN vectors are designed to minimize this)
Adenovirus Structure
Lentivirus Structure
Adenovirus Versus Lentivirus Downstream Considerations For Gene Therapy
The most common reasons why researchers choose between adenovirus and lentivirus as their viral vector is because of their unique characteristics for gene delivery. Both vectors have positive and negitive attributes in gene delivery which are important depending on the desired outcome for host gene modification.
Adenovirus Considerations:
- Expression duration: Typically transient (days to weeks) due to immune clearance
- Immunogenicity: High, often elicits strong innate and adaptive immune responses
- Target tissue: Broad tropism which is excellent for liver, respiratory epithelium, and many dividing/non-dividing cells
- Manufacturing: Generally higher titers and better stability
- Safety profile: Main concerns include inflammatory responses and pre-existing immunity in humans
Lentivirus Considerations:
- Expression duration: Long-term or permanent due to host cell genomic integration
- Immunogenicity: Lower than adenovirus and reduced immune response
- Target Tissue: Can transduce both dividing and non-dividing cells; requires pseudotyping for tissue specificity
- Manufacturing: Lower titers and more complex production. Read more about lentivirus titer.
- Safety profile: Main concerns include insertional mutagenesis risk and potential for RCL (replication-competent lentivirus)
Adenovirus Packaging vs Lentivirus Packaging
Our viral vector team can package both adenoviral vectors and lentiviral vectors, however there are significant differences between the two processes despite them both including plasmid transfection systems, packaging/helper cell lines, and ultracentrifugation for purification.
Adenovirus Packaging:
- Uses HEK293, HEK293T, or PER.C6 cells (containing E1 genes). Our team recommends HEK293T cell lines for increased titer levels. Read more about adenovirus packaging cell line.
- Often uses linearized plasmids or viral DNA.
- Produces viral particles through cellular lysis.
- Uses CsCl gradients or column chromatography for purification.
- Typically higher yields. Read more about adenovirus packaging and amplification for increased titer yield techniques.
Lentivirus Packaging:
- Uses 2-4 plasmid systems (transfer, packaging, envelope, and sometimes Rev) depending on lentivirus packaging generation.
- Viral particles bud from producer cell membrane. Read more about lentivirus packaging plasmids.
- Often pseudotyped with VSV-G for broad tropism.
- More sensitive to freeze-thaw and environmental conditions.
- Requires TET-OFF systems or other inducible promoters for safety.
Can The Same Plasmid DNA Construct Be Inserted Into An Adenoviral Vector And A Lentiviral Vector?
No, the same plasmid DNA construct cannot typically be used directly for both adenovirus and lentivirus productions and applications because of their capsid structure and viral elements including:
- Different packaging signals and regulatory elements: Adenovirus and lentivirus require distinct packaging signals and viral elements
- Size constraints: Lentiviral vectors accommodate less cargo
- RNA vs DNA genomes: Lentivirus requires elements for reverse transcription that adenovirus doesn’t need
- Architecture differences: Lentiviral vectors need LTRs and other retroviral elements
If you are interesting in editing your plasmid DNA transgene to be better suited for an adenoviral or lentiviral vector, our molecular cloning team can help.
Adenovirus vs Lentivirus Breakthrough Success In Viral Vector Therapeutics
Both adenovirus and lentivirus have had several clinical trial and commercial successes in the field of developing vaccine development, cell and gene therapy, and oncology treatments. These are just some of the latest breakthroughs for each viral vector.
Adenoviral Vector Successes:
- COVID-19 vaccines by AstraZeneca/Oxford
- Oncology therapies: Oncorine by Shanghai Sunway Biotech and ONCOS-102 by Oncos Therapeutics
- Genetic disease treatment Gendicine by Shenzhen SiBiono GeneTech Co. Ltd.
Ensuring the appropriate viral vector for your research is incredibly important. If you are not sure which viral vector is right for your research and development, contact our viral vector team.
Learn about our quick turnaround adenovirus packaging service and lentivirus packaging service.
Want to learn more about the latest in adenovirus or lentivirus based research? Our colleagues at ScienceDirect (adenovirus and lentivirus) and Genetic Engineering & Biotechnology News (adenovirus and lentivirus) continuously collect and publish the latest information on adenovirus and lentivirus based research.
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