About this Research Topic
Many diseases affect sensory organs with major clinical implications. Inherited diseases that affect the eyes (blindness) and ears (deafness) are commonly recognized disorders of the sensory system. However, there are other sensory disorders that affect the ability to smell, to sense pain, and to taste. In many of these cases there are no viable treatments or therapies that cure or greatly alleviate symptoms.
In the past decade gene replacement therapy for rare recessive diseases has made major progress, with many reports of therapeutic benefits in clinical trials for hemophilia, genetic blindness (Leber’s congenital amaurosis, LCA), and devastating neonatal neurological diseases, such as spinal muscular atrophy (SMA). Gene replacement/addition therapy involves adding a healthy, normal copy of the gene in addition to the two mutant alleles carried in the patient’s genome. Currently there are two FDA-approved gene therapies, using adeno-associated virus (AAV) vector-based therapies for LCA and SMA.
In some instances, particularly with dominant negative mutations, strategies using gene editing or knockdown are the most viable path to correct the pathology of the disease. Gene editing with systems such as zinc finger nucleases, CRISPR/Cas9, and meganucleases is a promising strategy to either eliminate expression of pathogenic genes or correct mutations. Recently, next generation genome editing technologies that take advantage of the Cas9 enzyme to anchor effector domains onto specific DNA targets have generated some promising therapeutic approaches. This idea has created several novel technologies, such as epigenome editors, base editors or prime editors. Using these, no double-stranded DNA break is required and often the gene editing outcome is more controlled.
While several groundbreaking studies have showed the potential of gene editing to correct diseases in preclinical models, there are many areas of the technology with room for improvement. Some of these areas that require characterization and development include:
- Vector systems capable of efficient cell delivery with the ability to carry the relatively large gene editing machinery or engineering smaller components
- Immunogenicity/toxicity of gene editing proteins
- Strategies to control or regulate expression of gene editing machinery to improve safety
For this topic, we are seeking a variety of manuscripts which address these and other issues surrounding gene editing in the context of sensory organs/tissues.
- Gene editing preclinical studies for diseases of the eye, ear and somatosensory system (including pain)
- Delivery modalities for gene editing systems targeting tissues of the eye, ear, nose, skin, tongue and somatosensory system
- Application of gene editing without DNA break (base editing, prime editing, epigenome editing)
- Defining target specificity and product heterogeneity of gene editing systems for sensory applications (DNA, RNA off-target)
- Toxicity, tolerability and immunity to gene editing systems
- General vector development for vision loss, hearing loss or pain (unless specifically for gene editing)
- Using high-throughput genome editing technologies to reveal disease associated molecular signatures and identify drug targets
- Gene editing of sensory disease genes in irrelevant cell lines (e.g. fibroblasts, HEK cells)
- Disease modelling with gene edited organoids, rodents etc.
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