Cell-specific aptamers for targeted therapies.
Many signalling proteins involved in diverse functions such as cell growth and differentiation can act as oncogenes and cause cellular transformation. These molecules represent attractive targets for cancer diagnosis or therapy and therefore are subject to intensive investigation. Aptamers are small, highly structured nucleic acid molecules, isolated from combinatorial libraries by a procedure termed SELEX. Aptamers bind to a target molecule by providing a limited number of specific contact points imbedded in a larger, defined three-dimensional structure. Recently, aptamers have been selected against whole living cells, opening a new path which presents three major advantages: (1) direct selection without prior purification of membrane-bound targets, (2) access to membrane proteins in their native conformation similar to the in vivo conditions and (3) identification of (new) targets related to a specific phenotype. The ability to raise aptamers against living cells opens some attractive possibilities for new therapeutic and delivery approaches. In this chapter, the most recent advances in the field will be reviewed together with detailed descriptions of the relevant experimental approaches.
Cerchia
Laura
L
Istituto per l'Endocrinologia e Oncologia Sperimentale G. Salvatore, Naples, Italy.
Giangrande
Paloma H
PH
McNamara
James O
JO
de Franciscis
Vittorio
V
D000818:Animals; D052157:Aptamers, Nucleotide / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002477:Cells / Q000187:drug effects; D003584:Cytological Techniques; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics / Q000494:pharmacology; D052156:SELEX Aptamer Technique / Q000379:methods*
D052157:Aptamers, Nucleotide; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D017430:Prostate-Specific Antigen