Related Experiment Video

Updated: Jun 1, 2026

Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
14:20

Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?

Published on: June 13, 2014

Site-specific PEGylation endows a mammalian ribonuclease with antitumor activity

Thomas J Rutkoski1, John A Kink, Laura E Strong

  • 1Department of Biochemistry, University of Wisconsin-Madison, WI, USA.

Cancer Biology & Therapy
|June 3, 2011
PubMed

Insights

PEGylation of bovine pancreatic ribonuclease A (RNase A) enhances its antitumor activity by increasing serum half-life and reducing sensitivity to cytosolic inhibitor protein (RI). This strategy shows potent tumor growth inhibition in vivo.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Mammalian ribonucleases show promise as cancer chemotherapeutic agents due to their ability to degrade RNA.
  • Their therapeutic potential is limited by sensitivity to cytosolic inhibitor protein (RI) and short serum half-life.

Purpose of the Study:

  • To investigate if site-specific poly(ethylene glycol) (PEG) conjugation can improve the efficacy of bovine pancreatic ribonuclease A (RNase A).
  • To assess the impact of PEGylation on RNase A's sensitivity to RI, serum half-life, and antitumor activity.

Main Methods:

  • Site-specific conjugation of PEG chains to RNase A.
  • Evaluation of RNase A's resistance to RI in vitro.
  • Assessment of RNase A's serum half-life and pharmacokinetic profile in vivo.
  • Testing the antitumor efficacy of PEGylated RNase A in a mouse xenograft model.

Main Results:

  • PEGylation enabled RNase A to evade RI, with effectiveness dependent on PEG chain characteristics and conjugation site.
  • In vitro antiproliferative activity was reduced by PEGylation.
  • PEGylated RNase A exhibited reduced renal clearance and an increased serum half-life in vivo.
  • Significant tumor growth inhibition was observed in mice treated with PEGylated RNase A.

Conclusions:

  • Strategic site-specific PEGylation can overcome limitations of ribonucleases as chemotherapeutic agents.
  • PEGylation enhances the in vivo efficacy of RNase A, demonstrating its potential as an antitumor agent.

Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Experimental RNAi02:15

Experimental RNAi

RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
Ribozymes02:47

Ribozymes

The term ribozyme is used for RNA that can act as an enzyme. Ribozymes are mainly found in selected viruses, bacteria, plant organelles, and lower eukaryotes. Ribozymes were first discovered in 1982 when Tom Cech’s laboratory observed Group I introns acting as enzymes. This was shortly followed by the discovery of another ribozyme, Ribonulcease P, by Sid Altman’s laboratory. Both Cech and Altman received the Nobel Prize in chemistry in 1989 for their work on ribozymes.
Ribozymes can be...
Riboswitches01:56

Riboswitches

Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...