Compositions, methods and systems for identifying candidate nucleic acid agent

Inventors

WANG, Jinpeng • Yang, Qin • Gong, Qiang

Assignees

APTITUDE MEDICAL SYSTEMS Inc

Abstract

The present disclosure provides compositions, methods and systems for generating nucleic acid agents having a desired property, such as a property for specifically binding to a target. More specifically, the present disclosure provides compositions, methods and systems for generating a pool of modified members comprising modified nucleic acid agents with an unlimited range of chemical diversity.

Core Innovation

The invention provides a method for generating a pool comprising a plurality of modified members. The method begins with providing a pool comprising kernel members, where each kernel member has partially double-stranded candidate nucleic acid agents immobilized to a solid support. Each partially double-stranded candidate nucleic acid agent includes a forward strand and a reverse strand longer than the forward strand, and the forward and reverse strands associate at least partially via base-pairing.

The invention continues by extending the forward strand of each partially double-stranded candidate nucleic acid agent by nucleotide polymerization using the corresponding reverse strand as a template. During extension, at least one modified nucleotide is incorporated into the forward strand to form modified candidate nucleic acid agents. Each modified member thus comprises a plurality of modified candidate nucleic acid agents immobilized to the solid support.

For each modified candidate nucleic acid agent comprised by any modified member, a corresponding identification nucleic acid agent is comprised by the same modified member. The identification nucleic acid agent enables amplification of its corresponding modified candidate nucleic acid agent, and the nucleic acid sequence of the candidate nucleic acid agents in any kernel member is different from that of the candidate nucleic acid agents in at least one other kernel member in the pool.

Claims Coverage

The provided independent claim covers one solid-support pool architecture with four inventive features: kernel members with partially double-stranded candidate nucleic acid agents, template extension incorporating modified nucleotides, co-compartment inclusion of an amplification-enabling identification nucleic acid agent, and sequence diversification across kernel members.

The claim coverage centers on a solid-support pool architecture in which kernel members contain partially double-stranded candidate nucleic acid agents, modified candidate nucleic acid agents are produced by template extension with modified nucleotides, and each modified member pairs each modified candidate with a corresponding identification nucleic acid agent that enables amplification, while maintaining sequence diversification across kernel members.

Stated Advantages

Documented Applications