Objectives: To devise a framework of factors that should shape early decision making around which disease area to target for a gene therapy, from both a payer and a manufacturer perspective. Methods: Case studies of currently approved gene therapies were reviewed (Development path, uptake, HTA, and commercial performance). We devised a draft framework of factors that influence commercial performance. This framework was pressure tested at an internal workshop, before being sent out for comment to five experts. Following external validation, we finalised the framework. Results: There was consensus that it is possible to devise a framework that can be used to predict uptake and likely challenges for gene therapies based on the disease area they are targeting in clinical trials. From a purely commercial standpoint, it was determined that a target disease should have the following characteristics: 1) the disease should be relatively prevalent in rare disease terms. 2) gene therapy should be administered as early in life as possible, with the potential for benefits to accrue over a full lifetime. 3) disease burden should be high. 4) healthcare resource use should be high, with significant cost-savings expected in those who receive a gene therapy. 5) current treatment options should be limited and offer challenging benefit: risk profiles. 6) treatments currently approved for the disease should be expensive, setting a precedent for high pricing and offering a simple like-for-like cost offset. Conclusions: By evaluating case studies of currently approved gene therapies, we have devised a framework for assessing the economic viability of disease areas that may be used by developers as part of early decision making.