4.0.docx - yanlue

guiltlesscyanΒιοτεχνολογία

3 Δεκ 2012 (πριν από 8 χρόνια και 8 μήνες)

353 εμφανίσεις

4.0

1.

Biotechnology is the use of scientific knowledge (biological processes, organisms, or systems)
and

recombinant DNA (Genetic Engineering) techniques to manufacture products intended to
improve the quality of human life and benefit humans such as pharmaceutical drugs, medical
treatments or biological products.

The science of biotechnology can be divided
into subdisciplines called red, white, green, and
blue.

Red biotechnology involves medical processes such as produce new drugs from organisms,

designing of organisms to produce antibiotics,

using stem cells to regenerate damaged human
tissues and perhaps
re
-
grow en
tire organs and engineering of genetic cures through genetic
manipulation.

White (or
gray)
is a
biotechnology involves industrial processe
s such as the production of
useful chemicals (fuels for vehicles) or destroying polluting chemicals from enz
ymes which
play role as industrial catalysts.

Green biotechnology applies to agriculture and involves such processes as the development of
pest
-
resistant grains or the accelerated evolution of disease
-
resistant animals, selection and
domestication of plant
s via

micropropagation
, designing of

transgenic plants

to grow under
specific environmen
ts in the presence (or absence) of chemicals. Green biotechnology might
produce more environmentally friendly solutions than traditional

industrial agriculture

such as
the engineering of a plant to express a

pesticide
, thereby ending the need of external

application of pesticides.

Blue biotechnology, rarely mentioned, encompasses processes in
marine and aquatic
environments, such as controlling the proliferation of noxious water
-
borne organisms.

Application of biotechnology in medicine field such as drug production and

pharmacogenomics contribute to drug development.
Pharmacogenomics is the stu
dy of how
the genetic inheritance of an individual affects his/her body's response to drugs and also the
relationship between pharmaceuticals and genetics. Pharmacogenomics able to produce drugs
that are adapted to individual's genetic using protein, enzym
es
and

RNA

molecules

that are
associated with specific genes and diseases. Pharmacogenomics maximize therapeutic effects
of drugs, decrease damage to nearby healthy cells, determine accurate and app
ropriate drug
dosages to prevent overdose. A better, safer, inexpensive vaccines also can be designed and
produced by organisms transformed by means of genetic engineering.




2.

Important tools and developments include genomics, proteomics, ligand
-
recept
or interaction,
signal transduction, rational drug design, biochips, and microarrays
.

Genomics and proteomics

are important tools and development that
enable the discovery of
new genes and proteins and the comparison of their levels in diseased cells,
normal cells, and
cells treated with compounds that vary in their efficacy and toxicity. Thus, they could prove
valuable in identifying new drug targets.

L
igand
-
receptor interaction

is a key

element in designing a drug to interact with a target. To
bind with the target, most drug molecules insert themselves into a functionally critical si
te of
the target protein based on key and

lock

theory. The molecule induces or
inhibits

the protein's
fun
ction. A

better understanding of the target's st
ructure and functionality is essential for
better therapeutics or ligands

that bind

to the target. Recently, a

better understanding of
protein structure and function has yielded sophisticated approaches to t
he generation and
optimization of drug candidates

S
ignal transduction

is a result from

t
he interaction of the extracellular growth factor with its
receptor
.

T
he activation of cell signaling pathways that lead ultimately to cell division, the
synthesis of new
proteins, and tumor progression, t
his cascade of events is known
as
signal
transduction
.

Epidermal growth factor (EGF)

is a

growth factor

that stimulates

cell growth
,

proliferation

and

differentiation

by binding to its receptor

EGFR
.

S
teps along

the epidermal growth factor
(EGF) pathway and potential places for pharmaceutical intervention
:

-

binding of EGF to EGF receptor induce
s dimerization of the receptor

-

activation
of receptor kinase activity

-

interaction of activated rece
ptor
with signaling enzymes

-

induction of deoxyribonucleic acid (DNA) synthesis
and transcription into mRNA

-

messenger RNA (mRNA) is translated to proteins important in inducing further
cell growth and survival.

Rational drug design

is a more focused approach, which uses information about the

structure
of a drug receptor or one of its natural ligands to identify or create candidate drugs. The three
-
dimensional structure of a protein can be determined using methods such as X
-
ray
cryst
allography or nuclear magnetic resonance spectroscopy.
Armed with this information,
researchers in the pharmaceutical industry can use computer programmes to search through
databases containing the structures of many different chemical compounds. The compu
ter
able to select those compounds that are most likely to interact with the receptor which can be
tested in the laboratory.
The first drug produced by rational design was Relenza, which is used
to treat influenza. Relenza was developed by choosing molecul
es that were most likely to
interact with neuraminidase, a virus
-
produced enzyme that is required to release newly
formed viruses from infected cells.


Many of the recent drugs developed to treat HIV infections (e.g. Ritonivir, Indinavir) were
designed to
interact with the viral protease, the enzyme that splits up the viral proteins and
allows them to assemble properly.

Another well
-
known drug that was produced by ligand
-
based design is Viagra. This drug was
designed to resemble cGMP, a ligand

that binds an enzyme called phosphodiesterase. By
blocking phosphodiesterase activity, it was hoped that the drug would help to relax the
vascular smooth muscle in the heart and therefore relieve the symptoms of angina. In clinical
trials, the effect of t
he drug on angina was not encouraging, but some of the male patients
developed erections.

http://genome.wellcome.ac.uk/doc_WTD020912.html


B
iochips

are a key technology that provide


mutationa
l analysis, gene sequencing, and protein
expression testing. They consist of many small arrangements called

microarrays

that contain
DNA

(deoxyribonucleic acid), ribonucleic acid (RNA)

or protein affixed to a small wafer
such as that used in computers. Each microarray, or chip, contains thousands of different
sequences of nucleotides or proteins. When a gene chip is reacted with a sample of unknown
nature, only complementary se
quences o
f DNA bind to the chip, u
nbound strands are washed
away. One illustration of a gene chip's utility is that by using a gene chip with different tumor
-
associated genes, it is possible to determine whether a mutant gene, or oncogene, is present in
a suspected

cancer cell.
Biochips are thus useful for identifying potential new drug targets.

For instance, DNA
-
based biochips have been used successfully for the detection of mutations
in specific genes as diagnostic "markers" of the onset of a particular disease

a
nd
to detect the
differences in gene expression levels in cells that are diseased versus those that are healthy.

http://www.nature.com/nbt/journal/v18/n10s/full/nbt1000_IT43.
html


Microarrays

is a collection of microscopic features (most commonly DNA) which can be

probed with target molecules to produce either quantitative (gene expression) or qualitative
(diagnostic) data. The initial production of arrays in the research arena included radiolabeled
macroarrays such as Southern blots and dot blots (
91
,

177
).

http://cmr.asm.org/content/22/4/611.full


This

is an orderly arran
gement of samples where matching of known and unknown DNA
samples is done based on base pairing rules. An array experiment makes use of common
assay systems such as microplates or standard blotting membranes. The sample spot sizes are
typically less than 2
00 microns in diameter usually contain thousands of spots.

Thousands of spotted samples known as probes (with known identity) are immobilized on a
solid support (a microscope glass slides or silicon chips or nylon membrane). The spots can
be DNA, cDNA, or
oligonucleotides. These are used to determine complementary binding of
the unknown sequences thus allowing parallel analysis for gene expression and gene
discovery. An experiment with a single DNA chip can provide information on thousands of
genes simultan
eously. An orderly arrangement of the probes on the support is important as the
location of each spot on the array is used for the identification of a gene.

Microarray
technology has extensive application in

Pharmacogenomics.
Comparative analysis of the
ge
nes from a diseased and a normal cell will help the identification of the biochemical
constitution of the proteins synthesized by the diseased genes. The researchers can use this
information to synthesize drugs which combat with these proteins and reduce t
heir effect.

http://www.premierbiosoft.com/tech_notes/microarray.html

Microscopic imaging

can enhance the drug discovery process by helping to describe how
disease processes unfold and how potential therapies might intervene.

Recently introduced
technologies, and enhancements to existing techniques, are addressing technical issues that
have li
mited the usefulness of microscopic imaging in the past, improving spatial resolution,
increasing tissue penetration, overcoming physical access issues and enhancing experimental
throughput. Notable recent trends

include the development of super
-
resolution

microscopes,
the incorporation of multiphoton techniques into intravital and fibre
-
optic microscopy and the
automation of microscopy and image analysis for high
-
content screening.

ht
tp://www.nature.com/nrd/journal/v7/n1/abs/nrd2446.html

http://www.liebertpub.com/ADT

http://www.sciencemag.org/site/products/drugdiscnew
.xhtml


3.

There are some companies investing more to solve problem facing througout drug
development process. Following are some examples.

-

Companies such as
Accelrys

and

Tripos

have developed computer

programs to
help the
synthetic molecules
designated to acquire
desired biological properties,
while minimizing the risks of such adverse effects as toxicity.

-

To reduce time consumed and increase the efficiency of locating possible drug
candidates, companies have developed large databases and powe
rful search
engines that allow researchers to enter the characteristics of a compound of interest
and search for natural or synthetic compounds with similar properties.
Accelrys,

ChemNavigator
, and

Sigma
-
Aldrich

provide scientists with the
searchable chem
i
cal databases
.
However, its disadvantage is

an excess of
information
.

-

C
ompanies such as LabBook and

ChemSW

offer specialized versions of
electronic laboratory notebooks to help scientists organize their information and
experimental data

to prevent information overload in system
.

-

GenVision and DNASTAR plug
-
in for Adobe Illustrator helps scientists visualize
expression data, functional comparisons and genome presentations.

-


P
harmaceutical and biopharmaceutical companies need to find ways t
o screen for potential
problems with promising molecules at the earliest possible stage. They also need to
streamline
the entire process so the
compounds that pass the screening move quickly along the
development pipeline.
G
enomic methods alone will not re
duce the cost and time of drug
development. Howev
er, other new developments
will help to improve the productivity of dr
ug
development such
as rational drug design, combinatorial chemistry, and in silico
experimentation via com
puters.

Current methods of ra
tional drug design accelerate discovery by removing some of the
randomness from the process. The methods involve the design and optimization of small
organic molecules based on either information derived from a protein structure or a small
collection of hi
ts from high throughput screening. Two things needed are: databases to hold
all the information that comes out of high throughput screening and various propri
etary
algorithms that allow
to dock compounds into the active sites you're targeting.

Roche scientists use rational drug design to examine what happens at the molecular level
when a drug binds with a receptor, thereby obtaining a three
-
dimensional picture of a binding
site. They aim to develop drugs that bind optimally to a given receptor w
ith greater selectivity,
thus improving efficacy. They also starting a program in metabolic diseases that involves lipid
metabolism. It is an example of their ability to do the in silico screening based on having a
very deep database from screening data ag
ainst the targets.

With the help from those approaches mentioned,
productivity

increasing indicates

screening
more samples in less time and with less labor. To acc
omplish this, manufacturers also

developed high throughput screening (HTS) systems that range

from semi automated work
stations to fully automated robotic system
s,
aim to provide consumables and reagents with
each piece of instrumentation for high throughput.

HTS products start out with liquid handling systems for the research laboratory, such as
multichannel pipetters, 96
-
well plate fillers, and washers produced by

Rainin

Instruments

and other firms. Eppendorf, meanwhile, recently introduced epMotion 5070, a
work station aimed at scientists who need flexibility in liquid handling.


At the other e
nd of the HTS range suppliers provide work stations that fill, wash and rinse,
and read fluorescence or other characteristics of a sample in addition to handling
liquids.

PerkinElmer

is among the leaders in laboratory automation and HTS, while

Applied

Bios
ystems
,

Beckman

Coulter
, and

Zymark

offer sophisticated robotic systems that are
even more versatile than work stations. Hamilton Company is developing high throughput
proteomics work stations for applications such as MALDI TOF MS target spotting
and
prote
in crystallization. Gary Engelhart, Hamilton's national sales manager said they

have been
working with

Data

Centric

Automation for a complete protein crystallization optimization
work station. Hamilton also offers flexible and sophisticated work stations,
automating assays,
and sample preparation during every phase of the drug discovery process.


M
icrowave energy

are focused as well

to speed up chemica
l reactions and increase yield.

The
technology, coherent synthesis, delivers highly reproducible results that are automatically
stored and made available to any chemist in the organization

Bioinformatics software plays a variety of roles in the general field of sequencing, including
ass
embling genomes and identifying genes and regulatory elements. Software also helps
investigators analyze similarities and differences between genes and org
anisms. Several dozen
companies
including

DNASTAR,

InforMax,

and

Nonlinear

Dynamics

are
create softwa
re
for manipulating genes and DNA sequences.


For instance, DNASTAR

makes the Lasergene suite. According to John Schroeder, vice
president of research and development at DNASTAR, this software performs many tasks:
sequence assembly and finishing, primer de
sign, gene discovery and annotation, sequence
pair and family alignment with phylogeny, restriction site analysis and mapping, a
nd protein
structure analysis.
Basically, Lasergene provides a wide range of functionality

and another
fact is
more than three t
housand research articles mention using this software.

Protein studies
often include data from

mass spectroscopy, protein chips, and two
-
dimensional gel electrophoresis. As a result, scientists need tools that keep track of data and
relate one data set to
another. Companies like

Amersham

Biosciences,

Bio
-
Rad,

and Oxfor
d
GlycoSciences offer such

products.

Protein separation by two
-
dimensional difference gel electrophoresis (DIGE) is one of
Amers
ham Biosciences's specialties. I
t's Ettan DIGE system
multiplexes dye molecules to
study more than one protein sample in a single gel and detects changes of as little as 10
percent in protein abundance levels. The DeCyder software package guides a user through a
DIGE exp
eriment and its analysis. DeCyder is
le
ading edge informatics application for 2D
processing, which means image processing, statistical ac
curacy, and experiment support.

The increasing scale of experiments also demands advanced infrastructure to keep up with
advanced approaches to proteomics. Th
e Scierra Laboratory Workflow Systems from
Amersham Biosciences provide data collection and analysis from various applications,
including sequencing, microarrays, a
nd proteomics.
This system tracks all of the components
involved in manufacturing data, and
it is
all integrated on one platform.

Integration also impacts the bioinformatics behind DNA and protein arrays. For
example,

Iobion

Informatics

makes GeneTraffic software for microarray analysis. Jason
Goncalves, cofounder and chief scientific officer at
Iobion, says essent
ially every step in
microarrays
from d
esigning them to analyzing them
requires informatics.


Ellen Beasley, director of b
ioinformatics at Celera says,
Bioinformatics is especially useful in
early stages of target identification and the d
rug
-
target validation process.

4.

During
500 B.C.E.
, first antibiotic of the world is

Moldy soybean curds(tofu) used to treat
boils (China).

First vaccination

discovered by
Edward

Jenner
during 1797 by take

pus from a cowpox lesion,

inserts it into an
incision on a boy's arm.

The very first enzyme is discovered and isolated during 1833 using biotechnological
techniques.



In 1982, Human insulin produced in genetically modified bacteria is the first biotech drug
approved by the FDA. The first biotechnology product approved for human health care was
synthetic human insulin, which came onto the market in the United States in 1
982.


First anti
-
cancer drug is produced through biotechnology when combined with interferon
u
singthe double agar layer method of human tumor clonogenic assay


http://www.unctad.org/en/do
cs/poitetebd10.en.pdf

http://www.ncabr.org/.../careersInBiomanufacturing_unit1_biotechTimeline

http://en.wikipedia.org/wiki/Biotechnology#Medicine