Novel Biotechnology Approaches in ENT Medicine
Next-generation sequencing (NGS) technologies have revolutionized the diagnosis and management of ENT disorders, particularly in genetic hearing loss, and represent the most significant biotechnological advancement in modern ENT practice. 1
Genetic Testing and Diagnosis
- NGS-based testing has replaced most single gene-sequencing tests for hearing loss, using disease-targeted exon-capture (targeted gene panel testing), exome sequencing (ES), or genome sequencing (GS) strategies to address genetic heterogeneity 1
- These technologies enable identification of variants in known hearing loss-related genes and potentially genes not yet associated with hearing loss, significantly improving diagnostic yield 1
- Targeted gene panels provide excellent coverage of selected genes but are limited by current knowledge, while ES/GS can detect variants in more genes but may have reduced analytical sensitivity in some genes 1
- Copy number analysis for detecting deletions/duplications should be considered as part of comprehensive genetic testing, as some panels may only interrogate sequence variants 1
Gene Therapy for Hearing Loss
- Gene replacement therapy using adeno-associated virus (AAV) vectors has shown promising results in animal models of hereditary hearing loss, with human clinical trials now underway 2, 3
- Recent clinical trials have demonstrated significant hearing improvement in treated patients, highlighting gene therapy's potential as a treatment for certain forms of genetic hearing loss 4
- The success of gene therapy depends on delivering corrective genes to proper targets within a therapeutic window, which may be unique for each specific defective gene 2
- Non-viral vectors (cationic lipids and polymeric nanoparticles) offer advantages including low immunogenicity and unlimited transgene size, though they're currently less efficient than viral vectors 5
Extracellular Vesicles in ENT Applications
- Mesenchymal stem cell-derived extracellular vesicles (EVs) can suppress inflammation caused by cochlear implantation and show promise in treating neurodegenerative diseases due to their anti-inflammatory properties 1
- Dendritic cell-derived EVs express MHC-I and MHC-II and are involved in antigen presentation, stimulating tumor-specific immune responses 1
- EVs can be used as drug delivery vehicles for siRNA, gene therapy, and conventional pharmaceuticals, offering targeted delivery to specific tissues 1
Growth Factors for Tympanic Membrane Repair
- Epidermal growth factor (EGF) and basic fibroblast growth factor (b-FGF) have shown remarkable success in tympanic membrane perforation closure, with rates up to 98.1% 6
- Application of growth factors with suitable scaffold materials after freshening perforation edges creates optimal conditions for healing 6
- Cartilage reconstruction demonstrates better structural outcomes with fewer postoperative tympanic membrane perforations compared to traditional temporalis muscle fascia grafts 7
Challenges and Future Directions
- Technical challenges in gene therapy include determining optimal routes of delivery to the inner ear, choice of vectors, promoters, and therapeutic strategies 3
- Current limitations of NGS technologies include inefficient capture of certain genomic regions and difficulties in detecting large deletions, duplications, and structural variations 1
- Development of noninvasive techniques for determining organisms present in middle ear effusions would facilitate appropriate microbiologic diagnosis and optimal treatment 1
- New diagnostic instruments with improved capacity for examination of the middle ear are needed, as even experienced otoscopists are accurate in diagnosing middle ear effusion in only approximately 80% of cases 1
Immunotherapy and Novel Biological Approaches
- GATA-3 DNAzyme, targeting the transcription factor essential for Th2 and ILC2 development, shows promise for treating nasal polyposis with potential for local nasal therapy 1
- Anti-siglec-8 therapies targeting eosinophils, mast cells, and basophils represent another emerging approach for inflammatory conditions in ENT 1
- Early studies suggest immunotherapy may improve symptom scores, objective endoscopic measures, and reduce the necessity for revision surgery in chronic rhinosinusitis patients 1
The integration of these novel biotechnologies into ENT practice promises to transform diagnosis and treatment, moving from symptomatic management to targeted, personalized interventions addressing the underlying causes of ENT disorders.