Evidence map›Paper›PMID 24285218›Full record

ArticleGene therapy2014

Suicide gene approach using a dual-expression lentiviral vector to enhance the safety of ex vivo gene therapy for bone repair.

F Alaee, O Sugiyama, M S Virk, H Tang, H Drissi, A C Lichtler, J R Lieberman

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Gene therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.6field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 29 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Gene therapy for bone healing: lessons learned and new approaches.Translational research : the journal of laboratory and clinical medicine · 2021
    Review
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. The challenges of promoting osteogenesis in segmental bone defects and osteoporosis.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2018
    Review
  15. Article
  16. Fixation stability dictates the differentiation pathway of periosteal progenitor cells in fracture repair.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2015
    Article
  17. Article
  18. Review
  19. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

F AlaeeDepartment of Orthopaedic Surgery, New England Musculoskeletal Institute, University of Connecticut Health Center, Farmington, CT, USA.
O SugiyamaDepartment of Orthopaedic Surgery, Keck School of Medicine at USC, Los Angeles, CA, USA.
M S VirkDepartment of Orthopaedic Surgery, New England Musculoskeletal Institute, University of Connecticut Health Center, Farmington, CT, USA.
H TangDepartment of Orthopaedic Surgery, Keck School of Medicine at USC, Los Angeles, CA, USA.
H DrissiDepartment of Orthopaedic Surgery, New England Musculoskeletal Institute, University of Connecticut Health Center, Farmington, CT, USA.
A C LichtlerDepartment of Genetics and Developmental Biology, School of Medicine, University of Connecticut Health Center, Farmington, CT, USA.
J R LiebermanDepartment of Orthopaedic Surgery, Keck School of Medicine at USC, Los Angeles, CA, USA.
UConn Health · USUniversity of Southern California · US

Funding

The Use of Regional Gene Delivery to Heal Critical Sized Bone DefectsR01AR057076 · NIAMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI LIEBERMAN, JAY R. · 2010 to 2021
$3.9M
NIAMS NIH HHS 1R01AR057076-01A1NIAMS NIH HHS R01 AR057076
6 · The paper itself

Abstract

'Ex vivo' gene therapy using viral vectors to overexpress BMP-2 is shown to heal critical-sized bone defects in experimental animals. To increase its safety, we constructed a dual-expression lentiviral vector to overexpress BMP-2 or luciferase and an HSV1-tk analog, Δtk (LV-Δtk-T2A-BMP-2/Luc). We hypothesized that administering ganciclovir (GCV) will eliminate the transduced cells at the site of implantation. The vector-induced expression of BMP-2 and luciferase in a mouse stromal cell line (W-20-17 cells) and mouse bone marrow cells (MBMCs) was reduced by 50% compared with the single-gene vector. W-20-17 cells were more sensitive to GCV compared with MBMCs (90-95% cell death at 12 days with GCV at 1 μg ml(-1) in MBMCs vs 90-95% cell death at 5 days by 0.1 μg ml(-1) of GCV in W-20-17 cells). Implantation of LV-Δtk-T2A-BMP-2 transduced MBMCs healed a 2 mm femoral defect at 4 weeks. Early GCV treatment (days 0-14) postoperatively blocked bone formation confirming a biologic response. Delayed GCV treatment starting at day 14 for 2 or 4 weeks reduced the luciferase signal from LV-Δtk-T2A-Luc-transduced MBMCs, but the signal was not completely eliminated. These data suggest that this suicide gene strategy has potential for clinical use in the future, but will need to be optimized for increased efficiency.

Indexed as

Genes, Transgenic, SuicideAnimalsBone Marrow CellsBone Marrow TransplantationBone Morphogenetic Protein 2Cell LineCombined Modality TherapyFemoral FracturesGanciclovirGenetic TherapyGenetic VectorsHumansLentivirusLuciferasesMaleMiceBone Morphogenetic Protein 2GanciclovirLuciferasesThymidine KinaseViral Proteins

Identifiers

PMID24285218
PMCPMC4896754
OpenAlexW2044187284

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.