Recombinant DNA has opened new horizons in medicine

The developments in gene manipulation that have taken place in the last 30 years have
revolutionized medicine by increasing our understanding of the basis of disease, providing new tools for
disease diagnosis, and opening the way to the discovery or development of new drugs, treatments, and
vaccines.
Progresele din domeniul manipulrii genelor care au avut loc n ultimii 30 de ani au revolu ionat
medicina prin....., oferind noi metode pentru diagnosticarea bolii i deschiz!nd calea pentru descoperirea
i sau dezvoltarea unor noi medicamente, tratamente i vaccinuri.
The first medical benefit to arise from recombinant "#$ technology was the availability of
significant %uantities of therapeutic proteins, such as human growth hormone &'('), which is used to
treat growth defects. *riginally '(' was purified from pituitary glands removed from cadavers.
'owever, many pituitary glands are re%uired to produce enough '(' to treat +ust one child. ,urthermore,
some children treated with pituitary-derived '(' have developed .reutzfeld/0akob syndrome
originating from cadavers. ,ollowing the cloning and e1pression of the '(' gene in E. coli, it became
possible to produce enough '(' in a 20-liter fermenter to treat hundreds of children. 3ince then, many
different therapeutic proteins have become available for the first time. 4any of these proteins are also
manufactured in E. coli but others are made in yeast or animal cells and some in plants or the milk of
genetically modified animals. The only common factor is that the relevant gene has been cloned and over
e1pressed using the techni%ues of gene manipulation.
Primul beneficiu din domeniul medical a fost apari ia tehnologiei $#"-ului recombinant a fost
disponibilitatea unor cantit i semnificative de proteine terapeutice cum ar fi hormonul de cre tere uman,
care este utilizat pentru tratarea defectelor de cre tere. 5ni ial hormonal de cre tere uman a fost purificat
din hipofizele scoase de la cadavre. Totu i, multe glande pituitare sunt necesare pentru a produce
suficient hormon de cre tere uman pentru a trata doar un singur copil. 6nii copii trata i cu hipofiza
derivat din hormonul de cre tere uman prelevat de la cadavre au dezvoltat .reutzfeldt-0akob. 7n urma
clonrii i modificrii genei de hormon de cre tere uman n 8. coli, a fost posibil s se produc sufficient
hormone ntr-un fermentator de 209 pantru a trata sute de copii. "in acel moment multe proteine
terapeutice diferite au devenit disponibile pentru prima oar. 4ulte din aceste proteine au fost ob inute n
culturi de 8.coli, altele sunt ob inute din culturi de dro+die, din celule animale sau vegetale modificate
genetic. 3ingurul factor comun este gena de interes care a fost clonat i e1primat folosind tehnici de
manipulare genetic.
4edicine has benefited from recombinant "#$ technology in other ways &,ig. 2.2). ,or
e1ample, novel routes to vaccines have been developed: the current hepatitis ; vaccine is produced by the
e1pression of a viral antigen on the surface of yeast cells, and a recombinant vaccine has been used to
eliminate rabies from fo1es in a large part of 8urope. (ene manipulation can also be used to increase the
levels of small molecules within microbial or plant cells. This can be done by cloning all the genes for a
particular biosynthetic pathway and over e1pressing them. $lternatively, it is possible to shut down
particular metabolic pathways and thus redirect intermediates towards the desired end product. This
approach has been used to facilitate production of chiral intermediates, antibiotics, and novel therapeutic
entities. #ew antibiotics can also be created by mi1ing and matching genes from organisms producing
different but related molecules in a techni%ue known as combinatorial biosynthesis. (ene cloning enables
nucleic acid probes to be produced readily, and such probes have many uses in medicine. ,or e1ample,
they can be used to determine or confirm the identity of a microbial pathogen or to carry out pre- or peri-
natal diagnosis of an inherited genetic disease. 5ncreasingly, probes are being used to determine the
likelihood of adverse reactions to drugs or to select the best class of drug to treat a particular illness in
different groups of patients. #ucleic acids are also being used as therapeutic entities in their own right.
,or e1ample, antisense nucleic acids are being used to downregulate gene e1pression in certain diseases,
and the relatively new phenomenon of <#$ interference is poised to become a breakthrough technology
for the development of new therapeutic approaches. 5n other cases, nucleic acids are being administered
to correct or repair inherited gene defects &gene therapy, gene repair) or as vaccines. 5n the reverse of
gene repair, animals are being generated that have mutations identical to those found in human disease.
These are being used as models to learn more about disease pathology and to test novel therapies.
4edicina a beneficiat de tehnologia $"#-ului recombinant n multe moduri. "e e1emplu s-au
dezvoltat noi rute la vaccinuri cum ar fi vaccinul hepatitei ; produs prin e1primarea unui antigen viral pe
celulele situate la suprafa a dro+diei i un vaccine recombinant utilizat pentru a elimina rabia la vulpi n
mare parte din 8uropa. (enele manipulate pot fi utilizate pentru a cre te nivelul moleculelor mici din
celula de origine microbian sau vegetal. $cest fapt poate fi realizat prin donarea tuturor genelor pentru
o cale biosintetic particular i pentru care le e1prim. 7n mod alternativ este posibil s se nchid
anumite ci metabolice i astfel redirec ionarea spre produsul final dorit. $ceast abordare a fost utilizat
pentru a facilita producerea de antibiotic i entit i terapeutice noi. #oile antibiotice pot fi create prin
amestecarea i potrivirea genelor de la microorganism care produc diferit dar moleculele sunt legate
printr-o tehnic cunoscut sub numele de biosintez combinatorie. .lonarea genelor permite probelor de
acid nucleic s fie produse cu u urin i s aib multe utilizri n medicin. "e e1emplu, ele pot fi
folosite pentru a determina identitatea unui agent patogen microbian sau pentru a efectua diagnosticul
bolilor mo tenite genetic pre- sau peri-natal. Tot mai mult, probele sunt folosite pentru a determina
probabilitatea reac iilor adverse lamedicamente sau pentru a selecta cea mai bun clas de medicamente
pentru a trata o anumit boal n diferite grupuri de pacien i. $cizii nucleic sunt folosite ca entit i
terapeutice de sine stttoare. 6n alt e1emplu, acizii nucleic antisens sunt utilizate pentru a reglementa n
+os e1presia genelor n anumite boli, iar fenomenul nou de interferen a $<#-ului este gata s devin o
tehnologie revolu ionar pentru dezvoltarea unor noi abordri terapeutice. 7n alte cazuri, acizii nucleic
sunt administrate pentru a corecta sau repara erorile genetice mo tenite &terapia genic, repararea gene)
sau ca vaccinuri. 7n reversul repara iei genice, animalele sunt generate