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[Safety evaluation of Ad-ASmyc in vitro and in vivo]
1Department of Abdominal Surgery, Cancer Hospital, Chinese Academy of Medical Science, Peking Union Medical College, Beijing 100021, China.
Objective:
To assess the safety of adenovirus-mediated transfer of anti-sense c-myc (Ad-ASmyc).
Methods:
RT-PCR was used to detect the transcription of Ad-ASmyc in HeLa cells infected with extracts from HeLa cells previously infected with Ad-ASmyc. Cell count was used to observe the effects of Ad-ASmyc on the growth of normal human fetal lung diploid cell line 2BS. Ad-ASmyc was given to 2 groups of Balb/c mice by intraperitoneal injection at a dosage of 10(7) pfu and 10(9) pfu respectively. Blood samples were obtained from the mice for liver and renal function tests. PCR was used to screen the vital organs for the presence of adenovirus DNA. Microscopic examination of the vital organs was performed to observe the pathogenicity of Ad-ASmyc.
Results:
As a replication-defective virus, Ad-ASmyc could infect 2BS cells effectively, but did not inhibit 2BS cell growth. No mouse died and no signs of general toxicity following intraperitoneal injection of Ad-ASmyc were observed. In mice injected with 10(9) pfu Ad-ASmyc, the adenoviral vector was found in the liver, spleen, kidney, and stomach. On day 6 and day 12 after injection, mild inflammatory infiltration of mononuclear cells was observed.
Conclusion:
The use ofadenoviral vector for antisense c-myc gene transfer in vitro and in vivo is considered to be safe for clinical trial.
Insights
Adenovirus-mediated transfer of antisense c-myc (Ad-ASmyc) showed no toxicity in cell lines or mice. This gene transfer method is safe for clinical trials.
Area of Science:
- Gene therapy
- Molecular biology
- Oncology
Context:
- Antisense c-myc gene therapy aims to inhibit tumor growth.
- Adenoviral vectors are common tools for gene delivery.
- Assessing the safety of novel gene therapy vectors is crucial before clinical application.
Purpose:
- To evaluate the safety and potential toxicity of adenovirus-mediated transfer of antisense c-myc (Ad-ASmyc).
Summary:
- Ad-ASmyc effectively infected human fetal lung diploid cells (2BS) without inhibiting growth.
- Mice receiving Ad-ASmyc via intraperitoneal injection showed no mortality or general toxicity.
- Adenoviral DNA was detected in multiple organs of mice, with mild mononuclear cell infiltration observed.
- Liver and renal function tests in mice did not reveal significant adverse effects.
Impact:
- Ad-ASmyc demonstrates a favorable safety profile in preclinical studies.
- The findings support the potential use of Ad-ASmyc in human clinical trials for cancer therapy.