Related Experiment Video

Updated: Feb 13, 2026

Acute and Chronic Models of Hyperglycemia in Zebrafish: A Method to Assess the Impact of Hyperglycemia on Neurogenesis and the Biodistribution of Radiolabeled Molecules
13:35

Acute and Chronic Models of Hyperglycemia in Zebrafish: A Method to Assess the Impact of Hyperglycemia on Neurogenesis and the Biodistribution of Radiolabeled Molecules

Published on: June 26, 2017

13.9K

Toxicology and Biodistribution: The Clinical Value of Animal Biodistribution Studies

Beatriz Silva Lima1,2, Mafalda Ascensão Videira1

  • 1Universidade de Lisboa, Faculdade de Farmácia, iMED.ULisboa, Lisboa 1649003, Portugal.

Molecular Therapy. Methods & Clinical Development
|March 16, 2018
PubMed

Insights

This review discusses the nonclinical development of gene therapy medicinal products (GTMPs), focusing on characterization, biodistribution, and safety evaluation. It highlights challenges and strategies for ensuring human safety from early development stages.

Area of Science:

  • Pharmacology
  • Genetics
  • Biotechnology

Background:

  • Advancements in human genome decoding increase understanding of genetic disturbances in diseases like cancer.
  • Gene therapy medicinal products (GTMPs) offer curative approaches by targeting gene correction.
  • Characterizing GTMPs presents unique challenges compared to conventional therapeutics.

Purpose of the Study:

  • To review and discuss nonclinical development requirements for GTMPs.
  • To address the needs and challenges in evaluating GTMP safety and efficacy.
  • To consider the utility and limitations of preclinical models for GTMPs.

Main Methods:

  • Review of existing literature and regulatory guidelines.
  • Comparative analysis of nonclinical development for GTMPs versus conventional drugs.
  • Discussion of biodistribution studies and their role in safety and efficacy assessment.

Main Results:

  • Biodistribution is crucial for GTMPs, informing safety and efficacy.
  • Nonclinical packages for GTMPs require careful construction to ensure human safety.
  • Conventional preclinical models have limitations for GTMP evaluation.

Conclusions:

  • Ensuring GTMP human safety necessitates tailored nonclinical development strategies.
  • Understanding vector and construct specificities is key to anticipating GTMP behavior.
  • European regulatory context provides valuable experience for GTMP development.
Keywords:
ATMPsadvanced therapy medicinal productsbiodistributiongene therapymodel relevancepreclinical programsrisk-based approach

More Related Videos

In Vivo Immunofluorescence Localization for Assessment of Therapeutic and Diagnostic Antibody Biodistribution in Cancer Research08:53

In Vivo Immunofluorescence Localization for Assessment of Therapeutic and Diagnostic Antibody Biodistribution in Cancer Research

Published on: September 16, 2019

9.6K
Utilizing an Orally Dissolving Strip for Pharmacological and Toxicological Studies: A Simple and Humane Alternative to Oral Gavage for Animals04:28

Utilizing an Orally Dissolving Strip for Pharmacological and Toxicological Studies: A Simple and Humane Alternative to Oral Gavage for Animals

Published on: March 23, 2016

13.2K

Related Concept Videos

Aneurysm II: Clinical Manifestations and Diagnostic Studies01:21

Aneurysm II: Clinical Manifestations and Diagnostic Studies

Thoracic, aortic arch and abdominal aneurysms are significant vascular conditions that can present with various clinical manifestations and lead to serious complications. Understanding these manifestations and the appropriate diagnostic studies is essential for effective management and treatment.Thoracic Aortic AneurysmsThoracic aortic aneurysms often remain asymptomatic until they reach a size that impinges on adjacent structures. They typically cause deep, diffuse chest pain that radiates to...
378
Hypertension III: Clinical Manifestations and Diagnostic Studies01:30

Hypertension III: Clinical Manifestations and Diagnostic Studies

Hypertension is asymptomatic and also referred to as the "silent killer" until it progresses to a severe stage or causes target organ disease. Patients may experience symptoms stemming from the strain on blood vessels and tissues in various organs or the heart's increased workload.Physical exams might show no abnormalities other than high blood pressure. Signs of vascular damage, when present, correspond to the organs supplied by the affected vessels, leading to target organ damage. For...
610
Venous Thrombosis II: Clinical Manifestations and Diagnostic Studies01:20

Venous Thrombosis II: Clinical Manifestations and Diagnostic Studies

The key difference between Superficial Vein Thrombosis (SVT) and Deep Vein Thrombosis (DVT) lies in their location and severity.Clinical ManifestationsSVT typically presents with localized pain, tenderness, and redness along the course of a superficial vein, often accompanied by a palpable, cord-like structure under the skin. This condition is usually less dangerous than DVT but can be uncomfortable and may lead to complications such as cellulitis or, rarely, a clot extension into the deep...
354
Rheumatic Heart Disease II: Clinical Manifestations and Diagnostic Studies01:22

Rheumatic Heart Disease II: Clinical Manifestations and Diagnostic Studies

The key clinical manifestations of Rheumatic heart disease (RHD) include several distinct cardiac symptoms.Carditis, a hallmark of acute rheumatic fever, involves inflammation of the heart's endocardium, myocardium, and pericardium. Chronic RHD often results from recurrent episodes of carditis. Its symptoms include the following:Murmurs are caused by valvular damage, especially to the mitral and aortic valves. Mitral stenosis or regurgitation is common, with characteristic heart murmurs...
667
Tonicity in Animals00:59

Tonicity in Animals

The tonicity of a solution determines if a cell gains or loses water in that solution. The tonicity depends on the permeability of the cell membrane for different solutes and the concentration of nonpenetrating solutes in the solution within and outside of the cell. If a semipermeable membrane hinders the passage of some solutes but allows water to follow its concentration gradient, water moves from the side with low osmolarity (i.e., less solute) to the side with higher osmolarity (i.e.,...
126.0K
Tonicity in Animals01:16

Tonicity in Animals

Tonicity describes the amount of solute in a solution. The measure of the tonicity of a solution, or the total amount of solutes dissolved in a specific amount of solution, is called its osmolarity. Three terms—hypotonic, isotonic, and hypertonic—are used to relate the osmolarity of a cell to the osmolarity of the extracellular fluid that contains the cells. In a hypotonic solution, such as tap water, the extracellular fluid has a lower concentration of solutes than the fluid inside...
5.4K