# Technology for measuring telomere length of individual chromosomes of single cancer cells

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $255,150

## Abstract

PROJECT SUMMARY/ABSTRACT:
 Telomere lengths and maintenance play very important roles in cancer, aging and other human diseases.
The lengths of human telomeres are known to be highly heterogeneous and variable for different cell types/age
and individuals, ranging from 0.5 kb to 20 kb in normal cells, and usually much shorter in most cancer cells. It
is also known that the shortest telomere, not the average telomere length, is critical for cell viability and
chromosome stability, and individual telomere length heterogeneity and telomere-driven genomic instability
may contribute to early carcinogenesis. However, the most common methods (TRF, qPCR and Q-FISH) for
telomere length measurements can only be used to estimate or infer the average length of the telomeres from
many cells with very limited sensitivity, resolution and accuracy. Even more surprisingly, none is capable of
measuring the length of the telomeres of all individual chromosomes and of single cells. The deficiency has
greatly hammered many telomere-related association studies and the use of telomere lengths as biomarkers
for clinical diagnosis of cancer and for prognosis of cancer treatments. To move the field of telomere biology
forward and to enable the routine clinical use of telomeres as cancer biomarkers, we need a scalable
technology for low-cost absolute length measurements of the telomeres of individual chromosomes in single
cells. In this project, we propose to develop a technology (TeloMeSeq) for measuring the absolute lengths of
the individual telomeres of all chromosomes in single human cells with single-nucleotide resolution in a
scalable and economic manner. We will leverage on our NEM-SDA (nicking endonuclease mediated strand-
displacement amplification) technology that has demonstrated to be capable of linear amplification of very
genomic DNA molecules independent of length to develop a one-tube procedure for the unbiased linear
amplification of all telomeres of single human cell and subsequent efficient sequencing library construction. We
will also leverage the powerful Pacific Biosciences' single-molecule real-time sequencing technology (PacBio
SMRT) that offers high throughput sequencing with very long reads (median read lengths > 20 kb) to sequence
the amplified telomeres in full length to identify the individual telomeres and to determine their lengths by
counting the number of telomere AATGGG repeats. We aim to demonstrate a proof of concept of the
TeloMeSeq technology using single cells from normal human leukocytes and IMR90 cell line, and cancer cell
lines (Jurkat and LNCaP). If successfully developed, our technology will enable the absolute length
measurements of all individual telomeres in single human cells with single-base resolution, far superior to
existing methods. Our TeloMeSeq technology has a great potential to transform telomere biology studies and
clinical practice where telomeres are used as biomarkers for cancer diagnosis and staging, aging and ot...

## Key facts

- **NIH application ID:** 9872995
- **Project number:** 5R21CA223727-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** XIAOHUA HUANG
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $255,150
- **Award type:** 5
- **Project period:** 2019-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9872995

## Citation

> US National Institutes of Health, RePORTER application 9872995, Technology for measuring telomere length of individual chromosomes of single cancer cells (5R21CA223727-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9872995. Licensed CC0.

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