MicroRNA-145 regulates oncolytic herpes simplex virus-1 for selective killing of human non-small cell lung cancer

Jhy-Ming Li1, Kuo-Chin Kao, Li-Fu Li

  • 1Department of Thoracic Medicine, Chang Gung Memorial Hospital, 5 Fu-Hsing Street, Kweishan, 333 Taoyuan, Taiwan.

Virology Journal
|July 24, 2013
PubMed
Abstract

Insights

A novel oncolytic herpes simplex virus-1 (HSV-1) engineered to target miRNA-145 shows promise for treating non-small cell lung cancer (NSCLC). This modified virus selectively kills NSCLC cells, offering a potential new therapy for this deadly disease.

Area of Science:

  • Oncolytic virotherapy
  • Molecular oncology
  • Gene therapy

Background:

  • Non-small cell lung cancer (NSCLC) presents a significant global health challenge, driving the need for innovative treatments.
  • Oncolytic virotherapy offers a promising strategy for advanced NSCLC.
  • MicroRNAs (miRNAs) play a role in regulating virus replication within tumors.

Purpose of the Study:

  • To investigate the potential of miRNA-145-regulated oncolytic herpes simplex virus-1 (HSV-1) for selective NSCLC treatment.
  • To assess the virus's ability to target NSCLC cells while minimizing damage to normal cells.

Main Methods:

  • Engineered HSV-1 (AP27i145) by incorporating miRNA-145 target sequences into the ICP27 gene.
  • Evaluated viral replication, target specificity, and toxicity in normal and NSCLC cells in vitro.

Main Results:

  • AP27i145 replication was inversely related to miRNA-145 expression levels.
  • The oncolytic HSV-1 demonstrated selective killing of NSCLC cells, inhibiting proliferation and colony formation.
  • Combined therapy with radiotherapy and AP27i145 significantly enhanced cancer cell killing.

Conclusions:

  • miRNA-145-regulated oncolytic HSV-1 represents a promising therapeutic agent for NSCLC.
  • This approach offers targeted cancer cell destruction with potentially reduced side effects.

Related Concept Videos

MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...
Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...
lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA (lncRNA)...