Gene Therapy Using Efficient Direct Lineage Reprogramming Technology for Neurological Diseases

Nanomaterials, 2023 · DOI: 10.3390/nano13101680 · Published: May 19, 2023

Simple Explanation

Gene therapy involves transferring genetic material into cells to treat diseases, showing promise for neurological conditions like paralysis, spinal cord injury, and Parkinson's disease. Direct lineage reprogramming (DLR) can treat incurable diseases but is less efficient than stem cell therapy. Researchers are exploring ways to improve DLR efficiency. Nanoporous particle-based gene delivery systems can enhance the reprogramming efficiency of DLR-induced neurons, potentially leading to more effective gene therapies for neurological disorders.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
AuNpRs (gold nanoporous rods) function as ROS scavengers in DLR, lowering internal cellular conversion stress and enhancing the efficiency of DLR-induced dopaminergic (iDA) neurons from brain astrocytes.
2
AuNpRs can be used not only as DLR accelerators but also as DLR transcriptional factor carriers, which could accelerate the DLR process without administrating viruses.
3
AAV-mediated gene therapy is a viable method for regulating the final cell type during in vivo reprogramming, which could lead to optimal therapeutic outcomes for central nervous system diseases.

Research Summary

Gene therapy, particularly using adeno-associated viruses, has shown significant progress in treating neurological diseases, including spinal cord injury and Parkinson’s disease, by targeting the delivery of therapeutic genetic fragments. Direct lineage reprogramming (DLR) offers advantages over conventional stem cell therapy, but its low efficiency hinders clinical application. Strategies to improve DLR efficiency, such as nanoporous particle-based gene delivery, are being explored. Nanotechnology, especially the use of nanoparticles like AuNpRs (gold nanoporous rods), can enhance DLR by acting as ROS scavengers and delivery vehicles for transcriptional factors, showing promise for treating neurological disorders by reducing cellular stress and improving therapeutic efficacy.

Practical Implications

Enhanced Gene Therapy

Improving DLR efficiency using nanoporous particle-based gene delivery systems can lead to more effective gene therapies for neurological disorders.

Targeted Drug Delivery

Nanoparticles, such as AuNpRs, can deliver growth factors or drugs to specific brain regions, minimizing toxicity to healthy neurons and improving cargo efficacy.

Spinal Cord Injury Treatment

In vivo DLR targeting of reactive astrocytes to convert them into motor neurons could provide a solution for paralysis in patients with SCI.

Study Limitations

1
Low efficiency and quality of reprogrammed cells in DLR-based gene therapy.
2
Concerns surrounding the use of AAV vectors, including AAV-induced autoimmune response and cargo size limitations.
3
Difficulty in obtaining sufficient cells for clinical translation using transcription factors in DLR due to low efficiency and lack of maturity.

Your Feedback

Was this summary helpful?

Back to Neurology