Risk assessment in human gene transfer studies

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Risk assessment in human gene transfer studies

• Stacey Berg, MD

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Types of gene transfer

• Ex vivo-
• Transfer genes with vector ex vivo
• Put altered cells in subject
• In vivo
• Put vector into subject
• Alter genes in vivo

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Types of risk

• Risk to personnel
• Production
• Care of subject
• Risk to subject
• Risk to bystanders

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Risks to personnel

• Production
• GMP facility
• Transport of agent to patient
• Administration of agent
• Containment
• Disposal of excess/equipment

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Risks to personnel

• Containment of subject
• Room or clinic
• Monitoring for viral shedding
• Contingency plans
• Waste handling/disposal

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Risks to subject

• Type of vector
• Transient v. stable transfection
• immunogenic
• Mode of administration
• Hepatic artery infusion, in vivo transfection
• Marrow ablation, ex vivo transfection
• Long-term
• Recombinant virus
• Insertional mutagenesis
• Germ-line alteration

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Risks to bystanders

• Family caregivers
• Off-spring
• Environment

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Why is gene transfer different?