Vision Restoration in Mice Through Genetic Editing and Music in DNA
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Chapter 1: Restoration of Vision in Mice
The retina, located at the back of our eyes, is an intricate biological structure. Within this vital area lies a molecule known as 11-cis-retinal. When light strikes the photosensitive section of the retina, this molecule transforms into all-trans retinal. This conversion initiates a series of chemical reactions that enable our brain to interpret visual information. However, for the cycle to continue, all-trans retinal must revert to its cis form, a process facilitated by the RPE65 protein. Unfortunately, mutations in the RPE65 protein can lead to inherited forms of blindness.
Recently, a study published in Nature Biomedical Engineering on October 19 revealed a breakthrough where researchers utilized a base editing protein that can modify specific nucleic acids in the genome without severing the DNA strands. By packaging this editor along with a guide RNA inside a virus and injecting it into the eyes of adult mice, they successfully corrected the mutation in the Rpe65 gene with an efficiency of up to 29%, while minimizing off-target mutations.
This video discusses a new gene-editing technique that has shown potential in reversing vision loss in mice.
Section 1.1: Cas9 Protein Size Reduction
Cas9, a widely used protein for DNA editing, presents challenges due to its significant size—2.5 times larger than hemoglobin and over 27 times bigger than an insulin protein. This size limitation complicates the delivery of Cas9 via small viruses for CRISPR therapy applications. Researchers from UC-Berkeley have recently introduced a method called MISER (Minimization by Iterative Size-Exclusion and Recombination) that allows for systematic testing of various deletions within the Cas9 protein to retain its editing capabilities. Remarkably, they succeeded in creating “minified” CRISPR proteins, with the smallest variant being just 874 amino acids long, which is about 60% the mass of the original Cas9 protein.
Section 1.2: Engineering E. Coli to Fix Carbon
In an intriguing development, a collaborative effort between UC-Berkeley and the Weizmann Institute of Science has enabled E. coli, a non-photosynthetic bacterium, to concentrate atmospheric carbon dioxide. By expressing twenty genes associated with carbon fixation, the engineered E. coli could grow by converting carbon dioxide from the air into biomass. This accomplishment not only sheds light on the carbon-concentrating mechanisms but also advances our comprehension of how carboxysomes operate.
Chapter 2: Genetic Engineering Insights
This video explores how new gene-editing techniques have been employed to restore vision in blind mice.
Reverse Engineering Pneumonia Pathogens
Pneumonia, often caused by the bacterium Streptococcus pneumoniae, poses significant health risks worldwide. Researchers at the University of Groningen have devised methods to manipulate genetic programs within this microbe. Their open-access study published in PNAS demonstrated successful rewiring of gene expression, particularly targeting the operon responsible for the bacterium's virulence factor. This innovative approach could enhance our understanding of how S. pneumoniae transitions from a harmless organism to a dangerous pathogen.
DNA Storage Innovations
Recent advancements in DNA data storage have made it possible to store significant amounts of digital information in this biological medium. A new study reported the successful storage of about 100 kB of digital sheet music from Mozart's string quartet, 'The Hunt', utilizing a parallelized DNA synthesis method. Despite the method's susceptibility to errors, all stored data was retrievable through sophisticated algorithms that reconstructed the information.
Rapid Insights and Future Directions
Research continues to unveil groundbreaking findings across multiple domains, including:
- Cas9 and Cas12a limitations are being addressed by employing the Cas3 enzyme for large genomic deletions in various bacterial species.
- Synthetic biology researchers are exploring the vast diversity of genetic materials beyond model organisms like E. coli.
- The development of biosynthetic pathways in engineered strains of bacteria could pave the way for new antibiotic discoveries.
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