Microbiology and Immunology

Cloning: Applications to biological problems WORLD OF MICROBIOLOGY AND IMMUNOLOGY

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phrenia and Alzheimer’s disease. While not yet conclusive, the

involvement of chronic bacterial infections in maladies that

have hitherto not been suspected of having a bacterial origin

will not be surprising.

Research efforts to prevent chronic bacterial infections

are focusing on the prevention of the surface adhesion that is

a hallmark of many such infections. Molecules that can com-

petitively block the sites to which the disease-causing bacteria

bind have shown promising results in preventing infections in

the laboratory setting.

See alsoBacteria and bacterial infection; Biofilm formation

and dynamic behavior; Immunity, active, passive and delayed

CJD DISEASE•seeBSE ANDCJD DISEASE

CLINICAL MICROBIOLOGY•seeMICROBIOLOGY,

CLINICAL

CLINICAL TRIALS, TYPES•seeMICROBIOLOGY,

CLINICAL

CLONING: APPLICATIONS TO

BIOLOGICAL PROBLEMSCloning: Applications to biological problems

Human proteins are often used in the medical treatment of var-

ious human diseases. The most common way to produce pro-

teins is through human cell culture, an expensive approach

that rarely results in adequate quantities of the desired protein.

Larger amounts of protein can be produced using bacteriaor

yeast. However, proteins produced in this way lack important

post-translational modification steps necessary for protein

maturation and proper functioning. Additionally, there are dif-

ficulties associated with the purification processes of proteins

derived from bacteria and yeast. Scientists can obtain proteins

purified from blood but there is always risk of contamination.

For these reasons, new ways of obtaining low-cost, high-yield,

purified proteins are in demand.

One solution is to use transgenic animals that are genet-

ically engineered to express human proteins. Genetargeting

using nuclear transfer is a process that involves removing

nuclei from cultured adult cells engineered to have human

genes and inserting the nuclei into egg cells void of its origi-

nal nucleus.

Transgenic cows, sheep, and goats can produce human

proteins in their milk and these proteins undergo the appropri-

ate post-translational modification steps necessary for thera-

peutic efficacy. The desired protein can be produced up to 40

grams per liter of milk at a relatively low expense. Cattle and

other animals are being used experimentally to express spe-

cific genes, a process known as “pharming.” Using cloned

transgenic animals facilitates the large-scale introduction of

foreign genes into animals. Transgenic animals are cloned

using nuclear gene transfer, which reduces the amount of

experimental animals used as well as allows for specification

of the sex of the progeny resulting in faster generation of

breeding stocks.

Medical benefits from cloned transgenic animals

expressing human proteins in their milk are numerous. For

example, human serum albumin is a protein used to treat

patients suffering from acute burns and over 600 tons are used

each year. By removing the gene that expresses bovine serum

albumin, cattle clones can be made to express human serum

albumin. Another example is found at one biotech company

that uses goats to produce human tissue plasminogen activa-

tor, a human protein involved in blood clotting cascades.

Another biotech company has a flock that produces alpha-1-

antitrypsin, a drug currently in clinical trials for the use in

treating patients with cystic fibrosis. Cows can also be genet-

ically manipulated using nuclear gene transfer to produce milk

that does not have lactose for lactose-intolerant people. There

are also certain proteins in milk that cause immunological

reactions in certain individuals that can be removed and

replaced with other important proteins.

There is currently a significant shortage of organs for

patients needing transplants. Long waiting lists lead to pro-

longed suffering and people often die before they find the nec-

essary matches for transplantation. Transplantation

technology in terms of hearts and kidneys is commonplace,

but very expensive. Xenotransplantation, or the transplanta-

tion of organs from animals into humans, is being investi-

gated, yet graft versus host rejection remains problematic. As

an alternative to xenotransplantation, stem cells can be used

therapeutically, such as in blood disorders where blood stem

cells are used to deliver normal blood cell types. However, the

availability of adequate amount of stem cells is a limiting fac-

tor for stem cell therapy.

One solution to supersede problems associated with

transplantation or stem cell therapy is to use cloning technol-

ogy along with factors that induce differentiation. The

process is termed, “therapeutic cloning” and might be used

routinely in the near future. It entails obtaining adult cells,

reprogramming them to become stem cell-like using nuclear

transfer, and inducing them to proliferate but not to differen-

tiate. Then factors that induce these proliferated cells to dif-

ferentiate will be used to produce specialized cell types.

These now differentiated cell types or organs can then be

transplanted into the same donor that supplied the original

cells for nuclear transfer.

Although many applications of cloning technology

remain in developmental stages, the therapeutic value has

great potential. With technological advancements that allow

scientists to broaden the applications of cloning becoming

available almost daily, modern medicine stands to make rapid

improvements in previously difficult areas.

See also DNA hybridization; Immunogenetics; Microbial

genetics; Transplantation genetics and immunology

CLOSTRIDIUM•seeBOTULISM

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