VIEWS & RE-VIEWS

Exciting progress in the worlds of antibody and genetic engineering

Genetic engineering: An alternative and complementary approach to matching disease with defective genes exists. DNA sequences can be mutated in vitro then reintroduced into animals and the resultant disease observed.

Previously, investigators have used the technique of reverse genetics, now known as 'positional cloning'. This technique involves detecting the gene responsible for a particular pathological phenotype. However, it can be difficult to explain the phenotypic abnormalities of a disease from an isolated gene.

" , , The true clinical science of the next decade is going to rely on clinical observation, a knowledge of ",hich genes are looking for disease, and access to DNA facilities to fo/lo", our hunches'. Rces J. Forward dermatology. Ge nes looki ng for di seases. British Medical Journa l 304 590. 7 Mar 1992 ,,"

Antibody engineering: In the past, it has been difficult to produce human monoclonal antibodies. Now, phage antibody libraries " , , represent a ne", and potentially limitless source of readily accessible human antibodies against virtually any desired molecular target', These libraries can contain a complete human antibody repertoire and can be constructed by using antibody genes derived from immunised mice or humans with HIV infection. A library which is large and diverse enough to bypass the need for immunisation has been the most recent breakthrough. This library was constructed from the antibody genes of 2 healthy volunteers.

Artificial pairing of antibody variable domains on phage particles allows the constraints of the human immune system to be overcome. Genes can be randomly combined to create new artificial antibodies not represented in the human B cell population from which the genes are derived. These antibodies may be a great source of therapeutically useful antibodies as they are more likely to recognise human 'self components (many cancer antigens fall into the category of ' self). Automated production of human monoclonal antibodies may also be possible.

Research advances leading to the development of phage antibody libraries included the advent of phage antibodies. These are genetically engineered bacteriophage particles; they contain antibody genes with the corresponding antibody fragment displayed on their surface. Bacteria infected by these phage antibodies produce copious amounts of phage antibodies. Phage antibodies can therefore be selected for their ability to bind a specific antigen and can then be amplified by reinfection into bacteria. Russell 5.1 . Llewelyn MB. Hawkins RE. The human antibody library. Entering the nex t phage. British Medica l Journal 304: 585-586. 7 Mar

1992 "'"

/SSN 0156-2703/92/0321-0003/$1.00/0 'iii Adis International Ltd

5"

INPHARMA® 21 Mar 1992

VIEWS & REVIEWS

Exciting progress in the worlds of antibody and genetic engineering

Genetic engineering: An alternative and complementary approach to matching disease with defecti ve genes exists. DNA sequences can be mutated in vitro then reintroduced into animals and the resultant disease observed.

Previously, investigators have used the technique of reverse genetics, now known as ' positional cloning'. This technique involves detecting the gene responsible for a particular pathological phenotype. However, it can be difficult to explain the phenotypic abnormalities of a disease from an isolated gene.

' ... The true clinical science of the next decade is going to rely on clinical observation, a knowledge of which genes are looking for disease, and access to DNA facilities to follow our hunches'. Rces J. Forward dermatology. Genes looking for di seases. British Medical Journa l 304: 590. 7 Mar 1992 "'"

Antibody engineering: In the past, it has been difficult to produce human monoclonal antibodies. Now, phage antibody libraries ' ... represent a new and potentially limitless source of readily accessible human antibodies against virtually any desired molecular target'. These libraries can contain a complete human antibody repertoire and can be constructed by using antibody genes derived from immunised mice or humans with HIV infection. A library which is large and diverse enough to bypass the need for immunisation has been the most recen t breakthrough. This library was constructed from the antibody genes of 2 healthy volunteers.

Artificial pairing of antibody variable domains on phage particles allows the constraints of the human immune system to be overcome. Genes can be randomly combined to create new artificial antibodies not represented in the human B cell population from which the genes are derived. These antibodies may be a great source of therapeutically useful antibodies as they are more likely to recognise human 'self components (many cancer antigens fall into the category of ' self). Automated production of human monoclonal antibodies may also be possible.

Research advances leading to the development of phage antibody libraries included the advent of phage antibodies. These are genetically engineered bacteriophage particles; they contain antibody genes with the corresponding antibody fragment displayed on their surface. Bacteria infected by these phage antibodies produce copious amounts of phage antibodies. Phage antibodies can therefore be selected for their ability to bind a specific antigen and can then be amplified by reinfection into bacteria. Russell 5.1 . Llewel yn MB. Hawkins RE. The huma n antibody library. Entering the next phage. British Medical Journal 304: 585-586. 7 Mar

1992 "'"

/SSN 0156-2703/92/0321-0003/$1.00/0 "" Adis International Ltd

5

INPHARMA® 21 Mar 1992