Integration Site Profiling
Systematically detects AAV vector integration site distribution in the host genome and identifies potentially high-risk genomic regions near oncogenes or tumor suppressors.
Preclinical AAV Safety Validation
AAV Genome Integration Risk Assessment
Preclinical safety validation for AAV-mediated host genome integration - data-ready for your IND submission.
Core Advantages
Safety evidence for where AAV vector sequences integrate.
Designed for preclinical teams that need integration-site data, risk annotation, and traceable raw sequencing outputs for regulatory and program decisions.
IND-Ready Data Package
Reports are structured for regulatory safety sections and can support IND preparation with site statistics, genomic annotation, risk conclusions, and method notes.
Flexible Engagement
Embed the assessment into AAV Genome Optimization & Validation or AAV RUO Manufacturing, or order it as an independent safety evaluation.
Full Traceability
From raw sequencing data to final safety report, the audit path is preserved. BAM/CRAM files, integration site tables, and visualizations can be delivered together.
Safety Workflow
Integration-risk data is reviewed from sample intake to bioinformatics output.
Sequencing-oriented safety projects connect sample context, data processing, genomic annotation, and report review in one traceable path.
DNA sample contextSequencing dataSafety interpretation
Methods & Specifications
High-throughput sequencing plus bioinformatics risk annotation.
The method captures and localizes vector-sequence integration events in host genomic DNA, then annotates the result against reference genomes and safety-relevant genomic features.
Host Genome Integration Site Analysis
- Core method: host genome integration site analysis for AAV vector sequences.
- Uses high-throughput sequencing to capture and localize vector integration events.
- Designed to distinguish true genomic integration from episomal AAV genomes and technical noise.
- Detection sensitivity is evaluated by project according to sequencing depth, sample quality, and vector design.
- Specific library capture, primer design, and bioinformatics workflow details are not externally disclosed to protect methodology IP.
Safety Interpretation
- Integration sites are mapped to genomic coordinates such as GRCh38 or mm39.
- Genomic regions are annotated as genic, non-genic, regulatory, or high-risk contexts.
- Risk screens include nearby oncogene and tumor suppressor gene regions when applicable.
- Final reports include limitations and detection threshold statements for transparent review.
Sample Requirements
Project setup begins with treated DNA, controls, and vector sequence information.
Required Inputs
Matched control material improves background filtering and supports confident interpretation.
| Sample Type | Description | Requirement |
|---|---|---|
| AAV-treated cell or tissue DNA | Genomic DNA extracted from in vitro cells or animal tissues after AAV exposure. | Provide infection conditions, MOI, timepoint, tissue or cell type, and relevant experimental parameters. |
| Matched control sample | Untreated control cell or tissue genomic DNA. | Matched to treated samples for background noise filtering. |
| AAV vector sequence information | Full vector genome sequence from ITR to ITR. | Required to ensure assay specificity and avoid cross-reactivity. |
Sample shipping: customers can ship genomic DNA samples to the Crossilico laboratory through standard cold-chain logistics. Sample status is confirmed within 1 business day after receipt before analysis scheduling begins.
Bioinformatics Analysis
From sequencing reads to safety-ready integration profiles.
Analysis Outputs
Structured outputs are designed for review, visualization, and downstream regulatory writing.
| Analysis | Output | Description |
|---|---|---|
| Integration site localization | Genomic coordinate list | Precisely localizes integration events in supported reference genomes such as GRCh38 or mm39. |
| Integration frequency estimation | Read count and frequency per site | Estimates relative abundance of detected integration events. |
| Genomic region annotation | Genic, non-genic, and regulatory region distribution | Identifies whether integration sites occur near functional genomic regions. |
| High-risk site screening | Integration list near oncogenes or tumor suppressor genes | Core output for safety risk assessment. |
| Integration preference analysis | Genome-wide bias statistics | Evaluates whether the vector shows sequence or region preferences. |
| Visualization report | Genome circle map and integration distribution figures | Displays genome-wide distribution of integration events for direct review. |
Workflow
A clear five-step path from sample submission to consultation.
The visual structure matches the existing Crossilico service pages while emphasizing sequencing and bioinformatics milestones.
Customers submit genomic DNA samples plus vector sequence information. Crossilico confirms sample quality and experimental parameters.
Total timeline: 3-4 weeks after sample confirmation. Rush service can shorten the project to 2-3 weeks when rapid sequencing and accelerated bioinformatics analysis are available.
Deliverables
IND-ready safety documentation with raw data attached.
DeliverableFormatDescription
Safety Assessment ReportPDF
Integration site statistics, genomic region distribution, high-risk site list, risk conclusions, method description, and limitation statement.
Integration Site ListCSV / Excel
Complete coordinate list with frequency, genomic annotation, gene name, region type, and distance to nearest gene.
Raw Sequencing DataBAM / CRAM
Sequencing alignment files suitable for visualization and independent review in genome browsers such as IGV.
Structured DataJSON / CSV
Metadata-tagged data for computational pipelines or LIMS import.
Visualization FiguresPNG / PDF
Genome circle maps, integration site distribution plots, heatmaps, and region preference statistics.
Report template: the report structure is designed to align with common FDA and EMA IND expectations for gene therapy vector safety data and can be integrated into an IND submission package.
Use Cases
Where integration risk assessment supports decisions.
Preclinical Safety Assessment for IND Filing
Generate standardized integration site analysis reports that support the safety assessment section of AAV gene therapy IND submissions.
Vector Risk Profiling for GO/NO-GO Decisions
Compare integration risk profiles across candidate AAV vectors, serotypes, or genome designs to support pipeline prioritization.
Add-On to AAV Build Projects
Extend Crossilico AAV optimization or RUO manufacturing projects with safety data that integrates into the same final report package.
Independent Safety Validation
Use Crossilico as an independent third-party lab for objective integration risk evaluation of externally sourced or internally produced AAV vectors.
Build Service Integration
Use as an embedded safety module or as a standalone service.
Embedded in AAV Genome Optimization & Validation
- Add integration risk assessment on top of optimization and validation projects.
- Initiate safety analysis during the data assessment phase.
- Integrate optimization data and safety data into a unified druggability and safety package.
- Advantage: data consistency, synchronized timeline, and unified reporting.
Embedded in AAV RUO Manufacturing
- Add integration risk assessment within the RUO batch QC workflow.
- Complete safety validation before batch release when project scope requires it.
- Useful for long-term safety monitoring across multi-batch production programs.
- Advantage: batch-linked safety data for regulatory data packages.
Standalone Purchase
- Submit AAV products from any source for independent integration risk evaluation.
- Suitable for third-party audit, supplier evaluation, pipeline review, and regulatory communication support.
- Advantage: independent, objective, and fast to initiate.
FAQ
Common questions.
Is AAV genome integration a real risk for gene therapy?
While AAV is predominantly non-integrating and often persists as episomal DNA, rare integration events into the host genome have been documented. For regulatory submissions and clinical safety planning, integration profile evidence can be an important part of the safety package.
How is this service different from standard AAV characterization?
Standard AAV characterization measures physical vector quality such as titer, purity, and empty/full ratio. Integration risk assessment evaluates a biological safety question: whether and where vector sequences integrate into the host genome.
Can I add this to my existing AAV project with Crossilico?
Yes. If you are already working with us on AAV Genome Optimization or RUO Manufacturing, you can add Integration Risk Assessment before project completion. We recommend adding it during the data assessment phase so safety data can be integrated into the final report.
Can I order this as a standalone service for AAV from another supplier?
Yes. We accept samples from any source. You will need to provide the full AAV vector genome sequence and host genomic DNA extracted from AAV-treated cells or tissues, plus relevant infection conditions.
What type of samples do I need to provide?
The primary sample is genomic DNA extracted from AAV-infected cells or animal tissues. A matched untreated control sample is needed for background subtraction. If DNA extraction has not been completed, we can provide a protocol.
Is the report suitable for FDA/EMA IND submission?
Yes. The report structure is designed to align with typical gene therapy IND safety data expectations, including integration site distribution, frequency data, genomic annotation, and risk assessment conclusions.
How long does the analysis take?
Standard turnaround is 3-5 weeks from confirmed sample receipt. Rush service of 2-3 weeks is available when sequencing and bioinformatics capacity allow.
What data formats do you deliver?
Standard delivery includes a PDF report, CSV integration site list, BAM or CRAM raw sequencing files, and PNG/PDF visualizations. Custom JSON with metadata is available upon request.
Can you analyze samples from animal models other than rodents?
Yes. We can analyze samples from any host species for which a reference genome is available, including mouse, rat, non-human primates, and pig. Contact us to confirm availability for less common species.
Can this detect integration events at very low frequency?
Sensitivity depends on sequencing depth, sample quality, and vector design. During project consultation, we assess sensitivity requirements and recommend an appropriate sequencing depth, then state detection limits in the final report.
Start Safety Assessment
Need AAV integration risk assessment?
Submit your sample details for a free feasibility and project consultation. Standalone or bundled with your AAV project - flexible to your needs.