# Ligand Guided Selection of Aptamers against Human Leukemia and Lymphoma

> **NIH NIH SC1** · HERBERT H. LEHMAN COLLEGE · 2020 · $371,250

## Abstract

Abstract
Functional synthetic DNA or RNA ligands, known as aptamers, are a class of molecules
with the versatility and tunable pharmacokinetics required for disease detection and
therapy. The process by which aptamers are selected is called SELEX (Systematic
Evolution of Ligands by EXponential enrichment). SELEX is a screening technology that
allows the selection of oligonucleotide ligands against a variety of target molecules via
an iterative and evolutionary process of continuous enrichment. A number of aptamer
selection methods have become available to select aptamers against cell-surface
proteins. Thus far, however, none of these methods has successfully identified aptamers
specific to an antigen of a cell-surface receptor at its endogenous level and native
conformation. Such precise targeting of known proteins is a determinant of successful
diagnostic and therapeutic applications. Therefore, to select aptamers against the
predetermined site of a cell-surface receptor in its native state, we, for the first time,
introduced a simple method called Ligand-guided Selection (LIGS). Essentially, the
iterative process in conventional SELEX is designed to winnow out low-affinity binders
through a competitive process whereby high binders move on through the selection
process. LIGS exploits this step by introducing a stronger, known high-affinity ligand
against the target of interest to achieve two purposes: 1) directly outcompete and
replace aptamers specific towards the target of interest and 2) introduce structural
changes on the target protein upon binding of a secondary ligand to outcompete specific
aptamers. Based on the specificity of a natural pre-existing ligand towards its target, the
aptamers identified by LIGS are expected to show higher specificity towards the target
ligand. This method is simple and adaptable to a number of platforms, including phage-
display libraries and peptide libraries. Thus, the goal of this proposal is to further expand
the LIGS technology and to develop aptamer-based immunotherapeutic molecules. To
accomplish this, we will 1) identify a panel of aptamers against multiple surface markers
from an evolved cell-SELEX pool against B-cell lymphoma, 2) identify multiple aptamers
against overlapping regions of multidomain receptor sites of TCR-CD3 complex, and 3)
develop an antibody mimetic by post-SELEX modification, followed by engineering
dimeric aptamer constructs.

## Key facts

- **NIH application ID:** 9878882
- **Project number:** 5SC1GM122648-04
- **Recipient organization:** HERBERT H. LEHMAN COLLEGE
- **Principal Investigator:** Prabodhika Mallikaratchy
- **Activity code:** SC1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $371,250
- **Award type:** 5
- **Project period:** 2017-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9878882

## Citation

> US National Institutes of Health, RePORTER application 9878882, Ligand Guided Selection of Aptamers against Human Leukemia and Lymphoma (5SC1GM122648-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9878882. Licensed CC0.

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