Method for generating aptamers with improved off-rates

摘要

The present disclosure describes the identification and use of aptamers and photoaptamers having slower dissociation rate constants than those obtained using previously described methods. Specifically, the present disclosure describes methods for the identification and use of aptamers to one or more targets within a histological or cytological sample, which have slow rates of dissociation. The aptamers may be used to assess localization, relative density, and presence or absence of one or more targets in cytological and histological samples. Targets may be selected that are specific and diagnostic of a given disease state for which the sample was collected. The aptamers may also be used to introduce target specific signal moieties. In addition to target identification, the aptamers may be used to amplify signal generation through a variety of methods.

主权项

1. A method for the diagnosis of a specific disease state in a tissue or cell sample comprising:
(a) contacting a tissue sample or cell sample with an aptamer, wherein the aptamer comprises at least one C-5 modified pyrimidine that increases the dissociation half-life of the aptamer compared to the aptamer without the C-5 modified pyrimidine; (b) measuring the presence, absence or quantity of the aptamer; and (c) diagnosing the disease state of the tissue or cell based on the presence, absence or quantity of the aptamer measured.