Recombinant Adenoviruses for Delivery of Therapeutics Following Spinal Cord Injury

Frontiers in Pharmacology, 2022 · DOI: 10.3389/fphar.2021.777628 · Published: January 10, 2022

Spinal Cord Injury Pharmacology Genetics

Simple Explanation

Spinal cord injury (SCI) is a serious medical condition, often leading to disability and a signiﬁcant decrease in patients’ quality of life. Gene therapy is a promising approach, and recombinant adenoviruses (rAdVs) are frequently used as vectors to deliver therapeutic genes. This review discusses the advantages, limitations, and potential future uses of adenoviruses in treating spinal cord injuries.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
rAdV5-based vectors allow transduction of both nerve and glial cells, providing a high level of transgene expression.
2
rAdV5-based vectors with modiﬁed tropism may infect various cells used for SCI therapy.
3
The immunogenicity of ﬁrst-generation rAdVs signiﬁcantly limits direct administration of these rAdVs to the injury site.

Research Summary

Recombinant adenoviruses (rAdVs) are commonly used vectors in gene therapy for spinal cord injury (SCI) due to their ability to transduce various cell types and provide high transgene expression. The review highlights different generations of rAdVs, their delivery routes (direct, indirect, ex vivo), and transduction efficiencies in various cell lines used for SCI therapy. The review also addresses the immune response to rAdVs and the use of neurotrophic factors delivered by rAdVs for SCI therapy, emphasizing their potential to promote morphological and functional recovery.

Practical Implications

Optimize rAdV selection

Selecting the appropriate generation of rAdV based on the desired duration of transgene expression and potential immune response.

Targeted Delivery Methods

Employing retrograde administration or ex vivo gene therapy to minimize immune responses and enhance transgene expression in specific cell types.

Combination Therapies

Combining rAdV-mediated neurotrophic factor delivery with cell transplantation to maximize regenerative effects and functional recovery after SCI.

Study Limitations

1
Immunogenicity of first-generation rAdVs limits direct administration.
2
Short-term transgene expression with first-generation rAdVs may not be sufficient for long-term therapeutic effects in humans.
3
Effect of preexisting anti-AdV5 antibodies on the efficacy of adenoviral SCI therapy remains unclear.

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