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Related Concept Videos

Gene Therapy00:59

Gene Therapy

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Gene therapy is a technique where a gene is inserted into a person’s cells to prevent or treat a serious disease. The added gene may be a healthy version of the gene that is mutated in the patient, or it could be a different gene that inactivates or compensates for the patient’s disease-causing gene. For example, in patients with severe combined immunodeficiency (SCID) due to a mutation in the gene for the enzyme adenosine deaminase, a functioning version of the gene can be...
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Translation01:31

Translation

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Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of...
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Translation01:31

Translation

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Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Proteins are...
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Initiation of Translation02:33

Initiation of Translation

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Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
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Improving Translational Accuracy02:07

Improving Translational Accuracy

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Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
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Termination of Translation01:44

Termination of Translation

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The large ribosomal subunit has several important structures essential to translation. These include the peptidyl transferase center (PTC) - which is the site where the peptide bond is formed - and a large, internal, water-filled tube through which the nascent polypeptide moves. This latter structure is called the Peptide Exit Tunnel, and it begins at the PTC and spans the body of the large ribosomal subunit. During translation, as the nascent polypeptide chain is synthesized, it passes through...
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Related Experiment Video

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Less Invasive Light Irradiation Methods for Inner Ear Gene Therapy Based on Photoswitch Technology: Toward Clinical

Masao Noda1,2, Takahiro Otabe3,4, Ryota Koshu1

  • 1Department of Otolaryngology and Head and Neck Surgery, Jichi Medical University, Tochigi, Japan.

Human Gene Therapy
|February 4, 2026
PubMed
Summary
This summary is machine-generated.

This study demonstrates a novel gene therapy approach for hearing loss using light-activated Cre recombinase (PA-Cre) in mice. External auditory canal and tympanic membrane irradiation effectively activated gene expression in the cochlea, offering a minimally invasive method for inner ear gene therapy.

Keywords:
AAVgene therapyinner hair cellslight irradiationphotoswitch

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Area of Science:

  • Otolaryngology
  • Gene Therapy
  • Molecular Biology

Background:

  • Hearing impairment is a significant risk factor for dementia, and current treatments like hearing aids offer limited benefits.
  • Inner ear gene therapy presents a promising avenue for treating sensorineural hearing loss, but requires controllable and minimally invasive gene activation methods.
  • A photoactivatable Cre recombinase (PA-Cre) system was previously developed for spatiotemporal gene expression regulation.

Purpose of the Study:

  • To evaluate the feasibility of using external auditory canal (EAC) and tympanic membrane (TM) irradiation for minimally invasive activation of cochlear gene expression.
  • To assess the efficacy of a PA-Cre system delivered via adeno-associated virus vectors (AAV.GTX) for light-mediated gene activation in the mouse inner ear.
  • To compare the gene recombination efficiency of different light irradiation methods (direct cochlear, TM, and EAC) in the cochlea.

Main Methods:

  • Adeno-associated virus vectors (AAV.GTX) encoding PA-Cre and a Cre-dependent reporter were injected into the cochlea of C57BL/6J mice via the round window membrane.
  • Seven days post-injection, light irradiation was applied through three methods: direct cochlear access, TM fiber-optic probe, and noninvasive EAC irradiation.
  • Recombination efficiency in inner hair cells (IHCs) was quantified using whole-mount immunohistochemistry, measuring reporter gene expression (tdTomato).

Main Results:

  • AAV.GTX efficiently transduced IHCs and demonstrated low basal Cre activity (<5% tdTomato expression without light).
  • Direct cochlear irradiation achieved a high recombination rate (88.4 ± 1.5%).
  • TM and EAC irradiation resulted in comparable and high conversion efficiencies (95.8 ± 1.7% and 97.6 ± 1.2%, respectively), without compromising cochlear integrity.

Conclusions:

  • The PA-Cre system functions effectively in the mouse cochlea with minimal background activity.
  • Minimally invasive TM and EAC irradiation enable robust and controllable light-mediated gene activation in the inner ear.
  • This strategy provides a foundation for developing noninvasive, light-controlled gene therapy for hearing loss and other cochlear disorders.