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Technology Industry. Steve Jobs. Comment on this summary contact us here if you have any questions. Sign in to share your opinion. The kinds of basic biological diversity found in nature today, or those that have potentially evolved in the natural world and been tested for fitness over time, may have been and are still limited by certain natural constraints, including available building blocks—nucleotides and amino acids; natural mechanisms for generating genetic diversity; and, the strength and nature of selective pressures over time.

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Nor has there been enough time over the history of the earth for nature to have explored more than a tiny fraction of the diversity that is possible. Techniques have been developed to expand both the diversity of nucleotide or amino acid sequences of nucleic acids or proteins, respectively which in both cases ultimately hold the information specifying the folding and thus the conformation of biologically active molecules , or for creating a diversity of small molecules with different shapes, sizes, and charge characteristics.

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In addition, some investigators are creating unnatural nucleic acids and amino acids in order to test and explore possible structural constraints on molecules with biological function. All of these approaches result in novel types of genetic or molecular diversity that then require assessment of functional potential. This assessment typically takes the form of a screening process i.

While the technological processes of assessing and selecting molecules of interest—high-throughput screening and selection—have some features in common with the next category of technologies i. DNA synthesis is a technology that enables the de novo generation of genetic sequences that specifically program cells for the expression of a given protein.

It is not new, but technical enhancements continue to increase the speed, ease, and accuracy with which larger and larger sequences can be generated chemically. By the early s, scientists had demonstrated that they could engineer synthetic genes. Our ability to synthesize short oligonucleotides typically 10 to 80 base pairs in length rapidly and accurately has been an essential enabling technology for a myriad of advances, not the least of which has been the sequencing of the human genome.

The Genomics Age - How DNA Technology is Transforming the Way We Live and Who We Are

The past few years have seen remarkable technological advances in this field, particularly with respect to the de novo synthesis of increasingly longer DNA constructs. The chemical synthesis and ligation of large segments of a DNA template, followed by enzymatic transcription of RNA led to the de novo creation of the poliovirus genome in about 7, nucleotides in length , from which the infectious, virulent virus was res-. These studies raised concerns in the media that larger, more complex organisms, such as the smallpox virus which is approximately , base pairs long , might be within reach.

DNA synthesis technology is currently limited by the cost and time involved to create long DNA constructs of high fidelity as well as by its high error rate. Several recent studies have demonstrated important steps toward making gene synthesis readily affordable and accessible to researchers with small budgets, by decreasing its cost and improving its error rate. Almost simultaneously, another research group described a novel approach for reducing errors by more than fold compared to conventional gene synthesis techniques, yielding DNA with one error per 10, base pairs.

Developments in DNA synthetic capacity have generated strong interest in the fabrication of increasingly larger constructs, including genetic circuitry, 12 the engineering of entire biochemical pathways, 13 and, as mentioned above, the construction of small genomes. DNA synthesis technology could be used as an alternative method for producing high-value compounds. DNA synthesis technology could allow for the efficient, rapid synthesis of viral and other pathogen genomes—either for vaccine or therapeutic research and development, or for malevolent purposes or with unintentional consequences.

The proposal focuses on instrument and reagent licensing e. Classical genetic breeding has proven itself over and over again throughout human history as a powerful means to improve plant and animal stocks to meet changing societal needs. The late 20th century discovery of restriction endonucleases, enzymes that cut DNA molecules at sites comprising specific short nucleotide sequences, and the subsequent emergence of recombinant DNA technology provided scientists with high-precision tools to insert or remove single genes into the genomes of a variety of viruses and organisms, leading, for example, to the introduction of production-enhancing traits into crop plants.

The process is repeated for several generations. With DNA shuffling, sequence diversity is generated by fragmenting and then recombining related versions of the same sequence or gene from multiple sources e. Basically, it allows for the simultaneous mating of many different species. The result is a collection of DNA mosaics. The reassortment that occurs during the shuffling process yields a higher diversity of functional progeny sequences than can be produced by a sequential single-gene approach.

But chances are it never would have evolved. Evidence from at least one study shows that the best parent is not necessarily the one closest in sequence to the best chimeric offspring and thus would probably not represent the best starting point for single-gene evolution i. The technology has developed quickly, such that scientists are not just shuffling single genes, they are shuffling entire genomes.

In , biologists used whole-genome shuffling for the rapid improvement of tylosin production from the bacterium Streptomyces fradiae ; after only two rounds of shuffling, a bacterial strain was generated that could produce tylosin an antibiotic at a rate comparable to strains that had gone through 20 generations of sequential selection.

The Genomics Age: How DNA Technology Is Transforming the Way We Live and Who We Are

Despite continual improvements in the throughput of current screening procedures, the use of conditions that impose strong selective pressures for emergence of molecules with the desired properties is far more efficient in finding the most potent molecule in the pool. Ultimately, this rapid molecular method of directed evolution will allow biologists to generate novel proteins, viruses, bacteria, and other organisms with desired properties in a fraction of the time required with classical breeding and in a more cost-effective manner.

For example, virologists are using DNA shuffling to optimize viruses for gene therapy and vaccine applications. Bioprospecting is the search for previously unrecognized, naturally occurring, biological diversity that may serve as a source of material for use in medicine, agriculture, and industry. These materials include genetic blueprints DNA and RNA sequences , proteins and complex biological compounds, and intact organisms themselves.

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  • Humans have been exploiting naturally-derived products for thousands of years. Even as high-throughput technologies like combinatorial chemistry, described above, have practically revolutionized drug discovery, modern therapeutics is still largely dependent on compounds derived from natural products. Excluding biologics products made from living organisms , 60 percent of drugs approved by the Food and Drug Administration and pre-new drug application candidates between and were of natural origin.

    And aspirin—arguably one of the best known and most universally used medicines—is derived from salicin, a glycoside found in many species in the plant genera Salix and Populus. Bioprospecting is not limited to plants, nor is drug discovery its only application. Most recently, with the use of molecular detection methods, scientists have uncovered a staggering number of previously unrecognized and uncharacterized microbial life forms.

    Natural products discovered through bioprospecting microbial endophytes—microorganisms that reside in the tissues of living plants—include antibiotics, antiviral compounds, anticancer agents, antioxidants, antidiabetic agents, immunosuppressive compounds, and insectides.

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    With respect to the last, bioinsecticides are a small but growing component of the insecticide market. Bioprospected compounds exhibiting potent insecticidal properties include nodulisporic compounds for use against blowfly larvae isolated from a Nodulisporium spp. Prospecting directly for DNA and RNA sequences that encode novel proteins with useful activities has become a potentially important scientific and business enterprise. This approach entails searches based on random expression of thousands or millions of sequences, followed by screening or selection for products with desired activities.

    This kind of approach can synergize with the DNA shuffling technology described above. For example, Diversa Corporation San Diego, CA utilizes bioprospecting of microbial genomes to develop small molecules and enzymes for the pharmaceutical, agricultural, chemical, and industrial markets. The samples are collected from environments ranging from thermal vents to contaminated industrial sites to supercooled sea ice.

    Bioprospecting has also been applied to the discovery of microbial agents in efforts to better understand the diversity of microbes in the environment that might serve as human pathogens if provided the opportunity. It has been argued that by deliberately scrutinizing the kinds of vectors and reservoirs that exist in a local environment for previously unrecognized microbes, novel agents might be identified long before they are discovered to be human, animal or plant pathogens, thus providing early warning of potential disease-causing agents.

    One might consider both molecular and traditional cultivation-based approaches for examining hosts, such as fruit bats and small rodents, which are already known to serve as reservoirs for important human microbial pathogens Hendra and Nipah viruses, Borrelia spp. As described above, the potential benefits associated with the discovery of novel products and microbial genetic diversity are innumerable.

    Whereas DNA synthesis enables the acquisition of genetic sequence diversity, these techniques allow for the generation of libraries of chemical compounds having a diversity of shapes, sizes, and charge characteristics—all of which may be of interest for their varied abilities to interact with and bind to biologically active proteins or macromolecular complexes, thereby altering the biological properties of these proteins and complexes.

    Combinatorial chemistry techniques can be used to create a wide range of chemotypes or molecular motifs, ranging from large polycyclic compounds of a peptidic nature to smaller, presumably more druglike, compounds. Initially, it was believed that when used in combination with high-throughput screening technologies, combinatorial techniques would dramatically. While this has not yet proven to be the case, most pharmaceutical companies are still heavily invested in combinatorial chemistry and are exploring the development and implementation of novel methods to create additional libraries of compounds.

    A recent trend noted in the pharmaceutical industry is the move from the development of large, unfocused, general screening libraries to smaller, less diverse libraries for screening against a particular target or family of related targets. The origins of this new branch of chemistry can be traced back to the early s, when methods were developed for the solid-phase synthesis of peptides.

    The final polypeptide is released by chemically breaking its bond with the solid support and washing it free. This reduced the scale of the process and greatly facilitated the parallel synthesis of large numbers of peptides. A further modification of the technique enhanced the ability to create a diversity of peptide sequences by incorporating a combinatorial approach.