Gene Editing Prevents Blindness in Mice

A base editing protein was used, in mice, to prevent inherited retinal degeneration.

This is from Codon, my weekly newsletter. Subscribe for free.

Hello. A base editing protein was used, in mice, to prevent inherited retinal degeneration. A library of genetic parts is now available for engineering Mycoplasma, a type of microbe with a very small genome. And a gene therapy for a skin condition, hidden in skin cream, shows efficacy in a handful of people.

Engineered Photoreceptors

There is an inherited form of blindness, called Leber congenital amaurosis, that occurs in 2 or 3 children for every 100,000 births. That sounds like a small number, but it’s among the most common causes of blindness in children. Cells in the retina break down; problems with vision begin in infancy. Everything gets worse with time. Cone cells — specialized for color vision — stop working entirely. The condition often stems from a single mutation in a gene called RPE65.

All of this is awful. And soon, perhaps, preventable.

For a new study, mice carrying a mutation in RPE65 quickly lost their color vision. Their retinas degraded further with age. But injecting the animals with a base editing protein at 3 weeks of age prevented vision loss over time. The base editing protein flips a single A nucleotide and replaces it with a G, thus correcting the error in the RPE65 protein.

When the authors sequenced mRNA from the eyes of these animals, they found that the base editor ‘made the switch’ 82 percent of the time, although some other DNA sequences were also inadvertently altered.

In adult mice, the “base editing treatment restored approximately 36% of M-cone function and 30% of S-cone function,” the authors write, relative to untreated animals. Cone cells make up just two percent of all retinal cells, and so preserving even a few can make a big difference for vision.

Read more at Nature Communications.

Mycoplasma bacteria, which lack a cell wall and are thus resistant to many antibiotics, are also a tremendously good model organism. Mycoplasma genitalium have a genome with just 580,000 base pairs, about one-ninth that of E. coli. They were among the first cells to be sequenced (Haemophilus influenza was the first). And when the J. Craig Venter Institute decided to make a synthetic organism, basing their design on Mycoplasma seemed like an obvious choice.

Despite being a great model organism in principle, though, there are relatively few genetic tools to engineer Mycoplasma cells. A new study changes that, adapting three inducible systems — AraR from Bacillus subtilis, LacI from E. coli and the phage lambda CI system — specifically for Mycoplasma. Now, anyone can take these parts and build genetic circuits in this organism with ease.

Read more at Nature Communications.

Recessive dystrophic epidermolysis bullosa, or RDEB, is a skin condition that causes blisters, scars and open wounds. It’s caused by mutations in a gene called COL7A1, which helps to build collagen.

In a phase I/II clinical trial, researchers tested a skin cream loaded with a non-replicating form of the COL7A1 gene, packed into a herpes simplex virus shell. Nine people with RDEB were randomly sorted into a placebo or treatment group. After 12 weeks, their wounds were compared — the skin cream reduced the surface area of wounds, the duration that wounds were closed, and the time it took to close wounds.

Read more at Nature Medicine.

Other Papers

(* = open access, † = review article)

Basic Research

Persistence of plasmids targeted by CRISPR interference in bacterial populations. Mamontov V…Severinov K. PNAS. Link

*Laboratory evolution of synthetic electron transport system variants reveals a larger metabolic respiratory system and its plasticity. Anand A…Palsson BO. bioRxiv (preprint). Link

*CRISPRs in the human genome are differentially expressed between malignant and normal adjacent to tumor tissue. van Riet J…Louwen R. Communications Biology. Link


*Enhancing biofuels production by engineering the actin cytoskeleton in Saccharomyces cerevisiae. Liu H…Liu L. Nature Communications. Link

*Harnessing cellular perception apparatus for smart metabolic reprogramming. Tan C, Tao F & Xu P. bioRxiv (preprint). Link

OptDesign: Identifying Optimum Design Strategies in Strain Engineering for Biochemical Production. Jiang S…Krasnogor N. ACS Synthetic Biology. Link

De Novo Production of Plant 4′-Deoxyflavones Baicalein and Oroxylin A from Ethanol in Crabtree-Negative Yeast. Qian Z…Cai M. ACS Synthetic Biology. Link


*Synthetic cell–based materials extract positional information from morphogen gradients. Dupin A…Simmel FC. Science Advances. Link


*Metal-responsive regulation of enzyme catalysis using genetically encoded chemical switches. Zubi YS…Lewis JC. Nature Communications. Link

Cell-Free Technology

A Cell-Free Assay for Rapid Screening of Inhibitors of hACE2-Receptor–SARS-CoV-2-Spike Binding. Kikuchi N…Amit R. ACS Synthetic Biology. Link

*Characterizing a New Fluorescent Protein for Low Limit of Detection Sensing in the Cell-Free System. Copeland CE…Kwon Y. bioRxiv (preprint). Link

*DNA Input Classification by a Riboregulator-Based Cell-Free Perceptron. van der Linden AJ…de Greef TFA. ACS Synthetic Biology. Link

Computation & Models

*†Merging automation and fundamental discovery into the design–build–test–learn cycle of nontraditional microbes. Gurdo N, Volke DC & Nikel PI. Trends in Biotechnology. Link

*Nonmodular oscillator and switch based on RNA decay drive regeneration of multimodal gene expression. Nordick B…Hong T. Nucleic Acids Research. Link

CRISPR & Genetic Engineering

Fludarabine increases nuclease-free AAV- and CRISPR/Cas9-mediated homologous recombination in mice. Tsuji S…Kay MA. Nature Biotechnology. Link

A split prime editor with untethered reverse transcriptase and circular RNA template. Liu B…Sontheimer EJ. Nature Biotechnology. Link

*CRISPR-free base editors with enhanced activity and expanded targeting scope in mitochondrial and nuclear DNA. Mok BY…Liu DR. Nature Biotechnology. Link

*Enhancement of prime editing via xrRNA motif-joined pegRNA. Zhang G…Liu J. Nature Communications. Link

Genetic Circuits

*Building molecular band-pass filters via molecular sequestration. Zhang Y…Franco E. bioRxiv (preprint). Link

Medicine & Diagnostics

Gene therapy restores mitochondrial function and protects retinal ganglion cells in optic neuropathy induced by a mito-targeted mutant ND1 gene. Liu Y…Yu H. Gene Therapy. Link

Rapid cloning of antigen-specific T-cell receptors by leveraging the cis activation of T cells. Kobayashi E…Kishi H. Nature Biomedical Engineering. Link

*CAR T cells expressing a bacterial virulence factor trigger potent bystander antitumour responses in solid cancers. Jin C…Essand M. Nature Biomedical Engineering. Link

*Delivery of CAR-T cells in a transient injectable stimulatory hydrogel niche improves treatment of solid tumors. Grosskopf AK…Appel EA. Science Advances. Link

Isolation of mouse pancreatic islet Procr+ progenitors and long-term expansion of islet organoids in vitro. Wang J…Zeng YA. Nature Protocols. Link


CRISPR–Cas9-mediated chromosome engineering in Arabidopsis thaliana. Rönspies M…Puchta H. Nature Protocols. Link

Protein & Molecular Engineering

Massively parallel, computationally guided design of a proenzyme. Yachnin BJ…Khare SD. PNAS. Link

Tuning T cell receptor sensitivity through catch bond engineering. Zhao X…Garcia KC. Science. Link

*Translational recoding by chemical modification of non-AUG start codon ribonucleotide bases. Fujita Y…Asano K. Science Advances. Link

*Engineering functional membrane-membrane interface by InterSpy. Moghimianavval H…Ha T. bioRxiv (preprint). Link

Tools & Technology

*CRISPR-mediated multiplexed live cell imaging of nonrepetitive genomic loci with one guide RNA per locus. Clow PA…Cheng AW. Nature Communications. Link

†Optogenetic tools for microbial synthetic biology. Chia N, Lee SY & Tong Y. Biotechnology Advances. Link

*DiMeLo-seq: a long-read, single-molecule method for mapping protein–DNA interactions genome wide. Altemose N…Streets A. Nature Methods. Link


Bioinformatic Design of Dendritic Cell-Specific Synthetic Promoters. Johnson AO…James DC. ACS Synthetic Biology. Link

— Niko // @NikoMcCarty //