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Lives of the monster dogs
When a race of elegant, superintelligent dogs arrives in twenty-first-century New York, they become instant celebrities, but, unable to adjust to the modern world and confronted with an incurable disease, they construct a fantastic castle and barricade themselves inside.
Book
Enhancing Evolution
InEnhancing Evolution, leading bioethicist John Harris dismantles objections to genetic engineering, stem-cell research, designer babies, and cloning and makes an ethical case for biotechnology that is both forthright and rigorous. Human enhancement, Harris argues, is a good thing--good morally, good for individuals, good as social policy, and good for a genetic heritage that needs serious improvement.Enhancing Evolutiondefends biotechnological interventions that could allow us to live longer, healthier, and even happier lives by, for example, providing us with immunity from cancer and HIV/AIDS. Further, Harris champions the possibility of influencing the very course of evolution to give us increased mental and physical powers--from reasoning, concentration, and memory to strength, stamina, and reaction speed. Indeed, he says, it's not only morally defensible to enhance ourselves; in some cases, it's morally obligatory.
In a new preface, Harris offers a glimpse at the new science and technology to come, equipping readers with the knowledge to assess the ethics and policy dimensions of future forms of human enhancement.
eBook
Genetic engineering : science, technology, engineering
Readers will learn about the history of genetics from the initial discover of DNA to todays most incredible developments. They will also find out what role genetics are likely to play in upcoming technology and discover what it takes to make it in this fascinating field of science.
Book
CRISPR-Cas guides the future of genetic engineering
The diversity, modularity, and efficacy of CRISPR-Cas systems are driving a biotechnological revolution. RNA-guided Cas enzymes have been adopted as tools to manipulate the genomes of cultured cells, animals, and plants, accelerating the pace of fundamental research and enabling clinical and agricultural breakthroughs. We describe the basic mechanisms that set the CRISPR-Cas toolkit apart from other programmable gene-editing technologies, highlighting the diverse and naturally evolved systems now functionalized as biotechnologies. We discuss the rapidly evolving landscape of CRISPR-Cas applications, from gene editing to transcriptional regulation, imaging, and diagnostics. Continuing functional dissection and an expanding landscape of applications position CRISPR-Cas tools at the cutting edge of nucleic acid manipulation that is rewriting biology.
Journal Article
The unhappening of Genesis Lee
Seventeen-year-old Genesis Lee does not remember meeting Kalan even though she is a Mementi, a genetically enhanced human who should be able to remember everything perfectly.
Book
Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex
Systematic interrogation of gene function requires the ability to perturb gene expression in a robust and generalizable manner. Here we describe structure-guided engineering of a CRISPR-Cas9 complex to mediate efficient transcriptional activation at endogenous genomic loci. We used these engineered Cas9 activation complexes to investigate single-guide RNA (sgRNA) targeting rules for effective transcriptional activation, to demonstrate multiplexed activation of ten genes simultaneously, and to upregulate long intergenic non-coding RNA (lincRNA) transcripts. We also synthesized a library consisting of 70,290 guides targeting all human RefSeq coding isoforms to screen for genes that, upon activation, confer resistance to a BRAF inhibitor. The top hits included genes previously shown to be able to confer resistance, and novel candidates were validated using individual sgRNA and complementary DNA overexpression. A gene expression signature based on the top screening hits correlated with markers of BRAF inhibitor resistance in cell lines and patient-derived samples. These results collectively demonstrate the potential of Cas9-based activators as a powerful genetic perturbation technology.
The CRISPR-Cas9 system, a powerful tool for genome editing, has been engineered to activate endogenous gene transcription specifically and potently on a genome-wide scale and applied to a large-scale gain-of-function screen for studying melanoma drug resistance.
CRISPR-Cas9 used for gene-expression regulation
The CRISPR-Cas9 system has emerged as a powerful tool for genome editing and transcriptional regulation of specific genes. Feng Zhang and colleagues have successfully modified the system to specifically and potently activate endogenous gene transcription on a genome-wide scale, such that it can be used for large-scale functional genomics screens. Application to a genome-wide screen of melanoma cells for genes which when overexpressed can confer resistance to a BRAF inhibitor demonstrates the feasibility of such screens, and also led to the discovery of potential new resistance mechanisms.
Journal Article
Cloning and genetic engineering
This enlightening volume offers arguments for both sides of the cloning and genetic engineering debate.
Book
CRISPR, the disruptor
But although CRISPR has much to offer, some scientists are worried that the field's breakneck pace leaves little time for addressing the ethical and safety concerns such experiments can raise. The problem was thrust into the spotlight in April, when news broke that scientists had used CRISPR to engineer human embryos (see Nature 520, 593-595; 2015).
Journal Article
Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage
CRISPR/Cas9 DNA editing creates a double-stranded break in the target DNA, which can frequently generate random insertion or deletion of bases (indels); a new genome editing approach combining Cas9 with a cytidine deaminase is described here, which corrects point mutations more efficiently than canonical Cas9, while avoiding double-stranded breaks and indel formation.
DNA edits without double-helix breakage
The CRISPR/Cas technology widely used for genome editing involves formation of a double-strand break in the target DNA sequence. When used to modify a single nucleotide, this procedure frequently generates DNA insertions or deletions (indels). David Liu and colleagues describe an approach that obviates DNA cleavage, as a means to avoid such off-target mutations. This 'base editing' method, which utilizes a composite enzyme consisting of CRISPR/Cas9 and the APOBEC1 deaminase, can directly convert C to T (or G to A). They also describe modifications that increase the yield of the desired correction and significantly suppressing indel formation.
Current genome-editing technologies introduce double-stranded (ds) DNA breaks at a target locus as the first step to gene correction
1
,
2
. Although most genetic diseases arise from point mutations, current approaches to point mutation correction are inefficient and typically induce an abundance of random insertions and deletions (indels) at the target locus resulting from the cellular response to dsDNA breaks
1
,
2
. Here we report the development of ‘base editing’, a new approach to genome editing that enables the direct, irreversible conversion of one target DNA base into another in a programmable manner, without requiring dsDNA backbone cleavage or a donor template. We engineered fusions of CRISPR/Cas9 and a cytidine deaminase enzyme that retain the ability to be programmed with a guide RNA, do not induce dsDNA breaks, and mediate the direct conversion of cytidine to uridine, thereby effecting a C→T (or G→A) substitution. The resulting ‘base editors’ convert cytidines within a window of approximately five nucleotides, and can efficiently correct a variety of point mutations relevant to human disease. In four transformed human and murine cell lines, second- and third-generation base editors that fuse uracil glycosylase inhibitor, and that use a Cas9 nickase targeting the non-edited strand, manipulate the cellular DNA repair response to favour desired base-editing outcomes, resulting in permanent correction of ~15–75% of total cellular DNA with minimal (typically ≤1%) indel formation. Base editing expands the scope and efficiency of genome editing of point mutations.
Journal Article