# Self-assembled multifunctional aptamer-complex biomaterial for precision medicine

> **NIH NIH R01** · METHODIST HOSPITAL RESEARCH INSTITUTE · 2020 · $369,431

## Abstract

Project Abstract
 Self-assembled multifunctional aptamer-complex biomaterial for precision medicine
Oligonucleotide aptamers are a class of biomaterials that function as molecular ligands with high affinity and
specificity for a wide range of biological targets. Similarly to protein antibodies, aptamers bind to their cognate
targets via conformational recognition and thus, are often referred to as “chemical antibodies”. As small-sized
oligonucleotide biomaterials, aptamers can be rapidly synthesized and easily conjugated to various functional
agents for different clinical needs, and exhibit faster cancer-cell binding ability and deeper tumor-tissue
penetration than antibodies. The aforementioned features provide aptamers with notable advantages over
protein antibodies for clinical applications, and render them unique biomaterials for clinical use. Anaplastic large
cell lymphoma (ALCL) is the most common T-cell lymphoma in children. Biologically, lymphoma cells express
high-levels of the surface CD30 receptor, a signaling molecule regulating cell fate and a distinct biomarker for
ALCL diagnosis. Genetically, lymphoma cells express the Anaplastic Lymphoma Kinase (ALK) oncogene.
Currently, CHOP chemotherapy is the mainstay of treatment for ALK+ ALCL although is not ALCL cell-selective
or ALK gene-specific, and has serious adverse side effects.
To address these clinical challenges, we will develop a multifunctional aptamer-complex biomaterial through
self-assembly of functional oligonucleotides (aptamer and siRNA sequences) and self-loading of therapeutic
drugs. The formed aptamer-complex will act via three therapeutic modalities for simultaneous ALK+ ALCL cell-
targeted chemotherapy, gene therapy, and immunotherapy. We hypothesize that under CD30 aptamer
guidance, the aptamer-complex will specifically target ALCL cells and treat lymphoma through combination of
different cellular mechanisms, acting as (i) a chemotherapeutic killing lymphoma cells via cell-targeted drug
delivery, (ii) a gene therapeutic silencing ALK oncogene via aptamer-facilitated intracellular delivery of siRNA,
and (iii) an immunotherapeutic triggering apoptotic cell death via aptamer-mediated activation of cell CD30
signaling. To validate our hypothesis, the following studies will be conducted: To validate our hypothesis, the
following studies will be conducted: Aim 1: Formulation of self-assembled aptamer-complex biomaterial. Aim 2:
Functional validation of aptamer-complex. Aim 3: Preclinical study of aptamer-complex for precision therapy of
lymphoma. Aim 4: Preclinical pharmacokinetic and toxicity studies of aptamer-complex.
Technically, this study capitalizes on aptamer technology to develop a unique multifunctional biomaterial for
precision medicine. Scientifically, this study will provide a novel immunotherapeutic approach to treat ALCL by
stimulating cellular naïve apoptotic signaling via aptamer-mediated activation of CD30 receptors. Clinically, the
aptamer-complex will en...

## Key facts

- **NIH application ID:** 9836619
- **Project number:** 5R01CA224304-03
- **Recipient organization:** METHODIST HOSPITAL RESEARCH INSTITUTE
- **Principal Investigator:** Youli Zu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $369,431
- **Award type:** 5
- **Project period:** 2018-01-15 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9836619

## Citation

> US National Institutes of Health, RePORTER application 9836619, Self-assembled multifunctional aptamer-complex biomaterial for precision medicine (5R01CA224304-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9836619. Licensed CC0.

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