Format

Send to

Choose Destination
See comment in PubMed Commons below
Biotechniques. 2014 May 1;56(5):251-6. doi: 10.2144/000114167. eCollection 2014.

Lessons learned from vivo-morpholinos: How to avoid vivo-morpholino toxicity.

Author information

1
Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX; Biology of Physical Activity Laboratory, Dept. of Health & Kinesiology, Texas A&M University, College Station, TX.
2
Protein Chemistry Laboratory, Dept. of Biochemistry/Biophysics, Texas A&M University, College Station, TX.
3
Biology of Physical Activity Laboratory, Dept. of Health & Kinesiology, Texas A&M University, College Station, TX.

Abstract

Vivo-morpholinos are a promising tool for gene silencing. These oligonucleotide analogs transiently silence genes by blocking either translation or pre-mRNA splicing. Little to no toxicity has been reported for vivo-morpholino treatment. However, in a recent study conducted in our lab, treatment of mice with vivo-morpholinos resulted in high mortality rates. We hypothesized that the deaths were the result of oligonucleotide hybridization, causing an increased cationic charge associated with the dendrimer delivery moiety of the vivo-morpholino. The cationic charge increased blood clot formation in whole blood treated with vivo-morpholinos, suggesting that clotting could have caused cardiac arrest in the deceased mice. Therefore, we investigate the mechanism by which some vivo-morpholinos increase mortality rates and propose techniques to alleviate vivo-morpholino toxicity.

KEYWORDS:

annexin A6; blood clot formation; calsequestrin 1; vivo-morpholino

PMID:
24806225
PMCID:
PMC4182913
DOI:
10.2144/000114167
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Informa Healthcare, USA Icon for PubMed Central
    Loading ...
    Support Center