A history of genome engineering in popular culture (2023)

It was before DNA

H.G. Wells, the father of science fiction, was also a biologist by training. This is evident in his work.The Island of Dr. moreau(1896) where he explores the concepts of animal experimentation and modifications. The premise of the novel involves Dr. Moreau, who creates human-animal hybrids. This book is published 30 years afterThe seminal work of Gregor Mendelon genetic inheritance (1866) and just when theMendelian genetics was being revived by botanist Hugo de Vries(1896).

In 1928, Frederick Griffith usedmouse modelsto demonstrate thatesteotococos pneumoniabacteria can mutate from one organism to another. This is now famous asGriffith's experiment.

dna age

The period between 1940 and 1960 was crucial for genetics and science fiction. Scientists around the world began searching for the magic molecule that serves as the code for life. In 1944,O experimento de Oswald Avery, Colin MacLeod e Maclyn McCartyhe disproved the myth that protein is the carrier of genetic information and led to the crowning of DNA as the molecule of life. This was further reinforced by the discoveries of the 1952Experimento Hershey-Chase🇧🇷 In the same year, Rosalind Franklin and her student Raymond Gosling made the firstX-ray diffracted image of DNA🇧🇷 Finally, in 1953, Franklin along with James Watson and Francis Cricksolved the DNA double helix🇧🇷 In the 1960s, Har Gobind Khorana, Marshall W. Nirenberg and Robert W. Holley splitthe genetic codeand explained how the four letters of DNA are translated into the twenty amino acids. Once scientists established that DNA encoded all the information needed to regulate and propagate life, there was no going back.

While the world of molecular genetics was booming, science fiction saw the rise of literary giants like Isaac Asimov, Arthur C. Clarke, James Blish, and John W. Campbell. This period is calledGolden Age of Science Fiction, but the common themes these authors explored were space and robots. The warping of stars in spaceships and the emergence of murderous machines that exterminate all of humanity were the two most popular themes that sparked the imagination of most authors in this period.

Age of Genetic Engineering: Pre-CRISPR

Having visualized and understood DNA, the next milestone for the molecular biologist was to develop methods for manipulating it. TheThe term genetic engineering itself is attributed to science fiction writer Jack Williamson.who used it in his 1951 noveldragon island🇧🇷 In 1976, the world's first genetic engineering company,Genentech, was founded.

This commercialization of gene editing technology led to the development of many important medical and agricultural products. But it also made sci-fi director Ridley Scott wonder what would happen if these corporations went beyond genetic engineering to exploit humans. Ridley Scott directed Blade Runner (1982). It's a dystopian film that revolves around synthetic humans called replicants who are genetically engineered by a powerful corporation to serve as slaves.

meganucleasas

In 1989, the first DNA editing enzymes,meganucleasas, were discovered. These proteins are characterized bylarge DNA recognition sites, which makes them highly specific.

Jurassic Parkby Michael Crichton was published in 1990, just one year after the discovery of meganucleases. The story involves the resurrection of dinosaurs by extracting DNA from fossilized amber and supplementing it with DNA from living frogs through genetic engineering. The corresponding film was released in 1993 and the sequelsJurassic Park(1997, 2001, 2015, and 2018) were huge box office successes, signaling viewers' insatiable appetite for dinosaurs wreaking havoc in a theme park.

Launched in 1997,GATOis an American science fiction film starring Ethan Hawke, Uma Thurman and Jude Law. The name of the film itself is a combination of the four bases of DNA: A, T, G and C. In this film, Ethan Hawke's character rebels against the class division created by genetics.

zinc finger nucleases

zinc finger nucleases(ZFN) are artificial restriction enzymes generated by fusing a zinc finger DNA binding domain with a DNA cleavage domain (FokI). Zinc finger nucleases were first designed in 2005. The DNA binding domain can be designed to target specific DNA sequences, while FokI induces a double strand break. These breaks can then be repaired by homologous recombination with a repair template. Each zinc finger recognizes a triplet of nucleotides, and when multiple ZFNs bind, it can read many base pairs simultaneously toincrease specificity🇧🇷 This modular approach has made ZFNs very attractive to researchers.

SPEECH

Em 2010,transcription activator-type effector nucleases (TALEN)they were designed. TALENs follow a similar DNA binding and cleavage strategy as ZFNs, but instead of recognizing triplets of nucleotides, the components recognize single nucleotides. This confers TALENmore specificity and broader substrate preference than ZFNs.

Age of Genetic Engineering: Post CRISPR

CRISPR

The strategy of using a protein to recognize DNA sequences is not ideal. For first-generation gene editors, new amino acid recognition sites had to be designed every time we wanted to target new genomic sites. TheDiscovery of Cas proteins in 2005was a breakthrough in the world of genetic engineering, as CRISPR-Cas editing soon replaced the protein-based DNA-binding domain with aunique sequence of guide RNA🇧🇷 Cas proteins, like their predecessorinduce a double strand breakat the target genomic site. This is usually followed bynon-homologous end joinwhich results in the deletion of genes.

Star Trek - Beyond the Darkness(2013) which is the remake of the space melodramaStar Trek II:khan's wrath(1982) combined the worlds of genetic engineering and space travel. The film sees the USS.Companythe crew fights a genetically engineered Khan superhuman.

The soap opera,Inferno(2013) and the film version (2016) stars Tom Hanks as the protagonist (Langdon). The plot involves Langdon going after an anti-villain geneticist named Zobrist, who designs a virus that could potentially kill a third of humans (much like the Black Death).

basic editors

The main disadvantage of all endonuclease-based gene editors (meganucleases, ZFN, TALEN and CRISPR-Cas) is that they induce double-strand breaks (DSBs) in the genome. These technologies are based on the cellular DNA repair machinery, which can lead tohigh frequency of indel formationin the genome and are ineffective in introducing point mutations. In 2016, researchers at the Broad Institute envisioned a new strategy for introducing point mutations into the genome. They fused a catalytically altered Cas9 protein with a DNA-editing enzyme to generate theprototypic base-editing enzymes. Loscytidine base editors (CBE)use a cytidine deaminase to introduce a C→T change at precise locations in the genome. This was soon followed byAdenine Base Publishing Enzyme (ABE)in 2017. ABEs are based on a similar strategy to CBE, but use an ssDNA adenosine deaminase (evolved from a tRNA deaminase enzyme, TadA) toinduce an A→G mutationat the target genomic loci. Together, CBE and ABE prevented the rates of indel formation normally associated with DSBs and offered unprecedented prospects for curing diseases caused by single nucleotide variations in the genome.

Due to the rise of CRISPR in genetic engineering and the open publicity of the technology on various non-science platforms, CRISPR has also transcended the world of science fiction. This is evident in the use of the word 'CRISPR' for everything related to genetic engineering in recent science fiction films.uproar(2018), starring Dwayne "The Rock" Johnson, calls CRISPR a genetic engineering experiment gone horribly wrong. The film's plot involves The Rock and his supergiant albino gorilla fighting a monstrous wolf and an alligator, who have both been "crispr-affected".

first edition

The most recent advancement in genome editing ismain edition, What was itdesigned in 2019🇧🇷 It is based on a main editor which is a fusion between Cas9 and reverse transcriptase. Using an elongated template + guide RNA called a pegRNA (master-edit RNA), the master editor can install all possible point mutations, remove short stretches of DNA, and even insert new DNA at targeted genomic loci.

A Final Word on Representation of Genome Engineering in Pop Culture

SciFi is one of the most imaginative and important genres of literary fiction. It has always served as a vision of the future and to make us rethink our perspective of the present. While genome-editing technologies have sparked a renaissance in the fields of health, energy, and agricultural science, their portrayal in popular fiction has been largely negative. But these negative portrayals serve as a wake-up call for the entire scientific community, reminding us to always consider the ethics and broader implications of our research.

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Many thanks to our guest blogger Kartik Lakshmi Rallapalli at the University of California, San Diego.

Kartik Lakshmi Rallapalli is a third year student in Prof. Francesco Paesani at the University of California, San Diego. She is working in collaboration with Prof. Alexis Komor and together they are trying to further our understanding of base editing enzymes. Kartik's research focuses on using molecular dynamics simulations and machine learning to develop a predictive understanding of adenine base editors that can help accelerate the engineering of new base editor proteins. She is particularly interested in combining the realms of art and science. follow her@kartik_lakshmi.

Additional resources on the Addgene blog

• find moreCRISPR blog posts
• Learn more aboutCRISPR history
• read about othersgenome editing methods

Resources at Addgene.org

• visit ourCRISPR Guide
• MeetCRISPR plasmids for your research
• To browseplasmids for base editing

References

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