Medical Research Council

Celltech R&d Limited

The Babraham Institute

Michael S Neuberger

Julian Edward Sale

Rupert Christopher Landsdowne Beale

Sarah Jane Cumbers

Reuben Harris

Svend K Petersen-Mahrt

Marianne Bruggemann

Shunichi Takeda

Zizhen Yang

Cristina Rada

Terence Howard Rabbitts

Meng Wang

Kerstin B Meyer

Azim M Surani

The invention provides functional mutants of activation-induced cytidine deaminase (AID) protein that have increased activity as compared to a wild-type AID protein. The invention also provides nucleic acids encoding the functional AID mutants, and vectors and cells comprising the nucleic acids. The invention further provides methods of using the functional mutant AID proteins.

Mutants of activation-induced cytidine deaminase (AID) and methods of use

The invention is directed to a cell comprising a nucleic acid encoding an Activation Induced Deaminase (AID) polypeptide, a fusion protein comprising an AID polypeptide, and methods of using a nucleic acid encoding an AID polypeptide.

Activation induced deaminase (AID)

The present invention identifies that the expression of Activation Induced Deaminase (AID) or its homologues in cells confers a mutator phenotype and thus provides a method for generating diversity in a gene or gene product as well as cell lines capable of generating diversity in defined gene products. The invention also provides methods of modulating a mutator phenotype by modulating AID expression or activity.

Activation Induced Deaminase (AID)

The invention relates to a method for preparing an antibody-producing cell line capable of directed constitutive hypermutation of a specific nucleic acid region, comprising the steps of: a) screening a clonal cell population for V gene diversity; b) isolating one or more cells which display V gene diversity and comparing the rate of accumulation of mutations in the V genes and other genes of the selected cells; and c) selecting a cell in which the rate of V gene mutation exceeds that of other gene mutation.

Method for generating diversity

A process for the production of a chimeric antibody, comprising: a) preparing a replicable expression vector including a suitable promoter operably linked to a DNA sequence comprising a first part which encodes at least the variable region of the heavy or light chain of an Ig molecule and a second part which encodes at least part of a second protein; b) if necessary, preparing a replicable expression vector incuding a suitable promoter operably linked to a DNA sequence which encodes at least the variable region of a complementary light or heavy chain respectively of an Ig molecule; c) transforming an immortalized mammalian cell line with the or both prepared vectors; and d) culturing said transformed cell line to produce the chimeric antibody; chimeric antibodies produced by this process; and plasmids and transformed cell lines used in the process.

Production of chimeric antibodies

Chimaeric or wholly foreign immunoglobulin is obtained from cells or body fluid of a transgenic animal which has had inserted into its germline genetic material that encodes for at least part of an immunoglobulin, of foreign origin or that can rearrange to encode a repertoire of immunoglobulins, i.e. derived from a different animal source. For example, wholly human immunoglobulins may be produced from a transgenic mouse, possibly in response to an immunogen subsequently introduced to the mouse.

Production of antibodies from transgenic animals

Enhancers

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Cambridge, United Kingdom

Michael S Neuberger