Physicochemical stability and transfection efficiency of cationic amphiphilic copolymer/pDNA polyplexes for spinal cord injury repair

Scientific Reports, 2017 · DOI: 10.1038/s41598-017-10982-y · Published: August 17, 2017

Simple Explanation

This study explores a new method for delivering gene therapy to the spinal cord to help it heal after an injury. The method uses a special material called a cationic amphiphilic copolymer, or PgP, to carry DNA into cells. The PgP material is designed to protect the DNA from being broken down in the body and to help it get inside cells more easily. The researchers tested how well the PgP material worked in a rat model of spinal cord injury. They found that the PgP material was able to deliver DNA to the spinal cord and that the DNA was able to help the spinal cord heal. They also found that the PgP material was safe and did not cause any side effects.

Study Duration

6 Months

Participants

Sprague Dawley rats (male, 200 gm)

Evidence Level

Not specified

Key Findings

1
PgP/pDNA polyplexes exhibit increased stability in the presence of a competing anionic macromolecule (heparin) relative to bPEI.
2
PgP/pDNA polyplexes also maintained their transfection efficiency (83% relative to freshly prepared samples) after lyophilization when glucose was used as a cryoprotectant.
3
PgP/pβ-Gal polyplexes (N/P ratio of 30/1) injected in a rat T9 normal spinal cord were less cytotoxic than bPEI/pβ-Gal polyplexes (5/1) by TUNEL assay.

Research Summary

The study demonstrates that PgP can form polyplexes with pDNA that remain stable in the presence of competing polyanions and provide protection from serum nucleases. PgP/pDNA polyplexes can be stored for up to 4 months at 4 °C and maintain their transfection efficiency after lyophilization/reconstitution, important features for commercial and clinical application. PgP polyplexes injected intraspinally remain present in the local tissue for up to 5 days and achieve substantial beta-gal expression in the injured spinal cord and surrounding neural tissues.

Practical Implications

Improved Gene Delivery

PgP shows promise as a non-viral vector for delivering therapeutic genes to treat spinal cord injury, offering better stability and transfection efficiency compared to existing methods.

Clinical Translation Potential

The stability and shelf-life of PgP/pDNA polyplexes after storage and lyophilization enhance its potential for commercial and clinical applications in gene therapy.

Combinatorial Therapies

PgP's ability to carry hydrophobic drugs alongside genes opens opportunities for developing combination therapies targeting multiple aspects of SCI pathology.

Study Limitations

1
The study is limited to a rat compression SCI model, further research is needed to validate these findings in other animal models.
2
Long-term efficacy of PgP/pDNA polyplexes needs to be evaluated in preclinical animal models of SCI.
3
The cytotoxicity of PgP/pDNA was evaluated in the normal spinal cord. Further studies in the injured spinal cord are needed to address potential confounding effects of injury on cell viability.

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