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Consistent Delivery of Adeno-Associated Virus via Lateral Tail-Vein Injection in Adult Mice
Published on: August 23, 2024
Evaluation of biodistribution and safety of adenovirus vector containing MDR1 in mice
ZhenZhen Zhao1, Wei Liu, Yuxi Su
1Surgery and Oncology Laboratory, Pediatric Research Institution, Children's Hospital of ChongQing Medical University, ChongQing, China.
Background:
The aim of this study is to examine the safety and distribution of Ad-EGFP-MDR1, an adenovirus encoding human multidurg resistance gene (human MDR1), in the mice colon carcinoma model.
Methods:
After bone marrow cells (BMCs) were infected with Ad-EGFP-MDR1, they were administered by intra bone marrow-bone marrow transplantation (IBM-BMT). Total adenovirus antibody and serum adenovirus neutralizing factor (SNF) were determined. Biodistribution of Ad-EGFP-MDR1 was detected by in situ hybridization and immunohistochemistry. The peripheral hematocyte white blood cell (WBC), haemoglobin (Hb), red blood cell (RBC) and platelet (Plt) counts were analyzed.
Results:
Neither total adenovirus antibody nor SNF increased weeks after BMT. In situ hybridization and immunohistochemistry demonstrated concordant expression of human MDR1 and P-gp which were found in lung, intestine, kidney and BMCs after BMT, but not detected in liver, spleen, brain and tumor. No significant abnormality of the recovery hematocyte was observed on Day 30 after treatment.
Conclusion:
The results indicate that IBM-BMT administration of a replication defective adenovirus is a feasible mode of delivery, allowing exogenous transference. The findings in this study are conducted for the future long-term studies of safety assessment of Ad-EGFP-MDR1.
Insights
Intra bone marrow-bone marrow transplantation (IBM-BMT) of Ad-EGFP-MDR1 showed successful gene delivery to mouse tissues. This method is a feasible delivery mode for future Ad-EGFP-MDR1 safety studies.
Area of Science:
- Gene therapy
- Adenovirus vectors
- Cancer research
Background:
- Investigating Ad-EGFP-MDR1, an adenovirus encoding the human multidrug resistance gene (MDR1).
- Utilizing a mice colon carcinoma model to assess gene delivery.
- Evaluating the safety and distribution of the engineered adenovirus.
Purpose of the Study:
- To examine the safety and biodistribution of Ad-EGFP-MDR1.
- To assess the feasibility of intra bone marrow-bone marrow transplantation (IBM-BMT) for adenovirus delivery.
- To evaluate the expression of human MDR1 and P-glycoprotein (P-gp) post-transplantation.
Main Methods:
- Bone marrow cells (BMCs) infected with Ad-EGFP-MDR1 were administered via IBM-BMT.
- Adenovirus antibodies and neutralizing factors were measured.
- Biodistribution was assessed using in situ hybridization and immunohistochemistry.
- Hematological parameters (WBC, Hb, RBC, Plt) were analyzed.
Main Results:
- No increase in adenovirus antibodies or neutralizing factors was observed.
- Human MDR1 and P-gp expression was detected in lung, intestine, kidney, and BMCs.
- Expression was not found in the liver, spleen, brain, or tumor.
- No significant hematological abnormalities were noted by Day 30.
Conclusions:
- IBM-BMT is a feasible delivery method for replication-defective adenoviruses.
- Exogenous gene transference was successfully achieved.
- The study provides a foundation for future long-term safety assessments of Ad-EGFP-MDR1.
