Lentiviral Vectors Delivered with Biomaterials as Therapeutics for Spinal Cord Injury

Cells, 2021 · DOI: 10.3390/cells10082102 · Published: August 16, 2021

Simple Explanation

Spinal cord injury (SCI) is a severe trauma that leads to permanent disability and significant socioeconomic burden. Regenerative medicine aims to restore function after SCI using gene therapy and tissue engineering. Lentiviral vectors (LVs) and biomaterials have individually shown potential in promoting repair post-SCI in animal models. Combining these approaches appears to be more effective than using either alone. This review presents studies supporting the combined use of LVs and biomaterials in SCI therapies, summarizing methods to combine them to augment therapeutic effects.

Study Duration

Not specified

Participants

Animal models

Evidence Level

Review

Key Findings

1
Combining LVs with biomaterials enhances spatial control over LV delivery compared to bolus injection, improving transduction efficiency by placing the vector directly in the cell microenvironment.
2
Biomaterials improve viral stability and half-life, leading to more potent and sustained transgene expression. Some biomaterials shield LVs from the immune system, preventing immune-mediated inactivation and clearance.
3
The combination of LVs and biomaterials can be synergistic, targeting multiple obstacles to regeneration after SCI, leading to improved functional outcomes in animal models.

Research Summary

Spinal cord injury (SCI) presents a multifaceted pathophysiology, necessitating therapies that target various cellular and molecular mechanisms. Both biomaterials and lentiviral vectors (LVs) have demonstrated potential in promoting repair and functional restoration post-SCI in animal models. Studies suggest that a combination of biomaterials and LVs is more effective than either approach alone. This review summarizes methods to combine LVs with biomaterials for SCI treatment, aiming to demonstrate how LV delivery with biomaterials can augment both LV and biomaterial therapeutic effects in SCI. There is a growing body of work on the beneﬁcial properties of viral vector delivery with biomaterials for SCI treatment. LV delivery using biomaterials and/or LV-biomaterial combinational therapies can work synergistically leading to superior improvement in regeneration markers after SCI.

Practical Implications

Enhanced Therapeutic Efficacy

Combining LVs with biomaterials leads to superior regeneration markers after SCI due to synergistic effects.

Improved Vector Delivery

Biomaterials provide better spatial control and localization of LVs, increasing transduction efficiency.

Protection from Immune Response

Biomaterials can shield LVs from the immune system, preventing inactivation and clearance, thus prolonging therapeutic effects.

Study Limitations

1
Leptomeningeal ﬁbroblastic scar found at both ends of scaffold and impeded re-penetration of axons into white and grey matter
2
Speed of host cell infiltration is key in LV delivery on biomaterials. LVs have a relatively short half-life at body temperature
3
Direct linking of the VSV.G protein to biomaterial was found to also cause steric hindrance reducing transduction. This steric hindrance was relieved with addition of a linker peptide

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