A seed does not sprout overnight. It waits, it struggles, and only after storms and silence does a fragile shoot break the ground. Science, too, is like this full of uncertainty, resistance, and persistence before something new takes flight.
For Dr. Arun Srivastava, this has been a lifetime’s journey. From a humble background in India, he pursued a PhD in Microbiology at the Indian Institute of Science, carrying with him little more than curiosity and conviction. Early in his career, his attention turned to a small, obscure virus: Adeno-Associated Virus (AAV). At the time, the idea of using viruses to heal to deliver healthy genes into human cells was met with disbelief. Viruses were considered enemies, not tools.
Yet where others saw impossibility, Srivastava saw potential. He trusted his intuition that AAV could be repurposed as a safe courier for therapeutic genes. It was not an easy path recognition was slow, funding was scarce, and technical barriers were immense. But persistence became his compass.
AAV is a small, non-pathogenic virus. Unlike retroviruses, it does not integrate into the host genome, which means it can deliver therapeutic DNA without altering the genetic blueprint. In essence, AAV vectors act like molecular couriers, delivering corrected “sentences” into the body’s instruction manual the genome so that cells can function as intended.
This approach became the foundation of gene therapy, a radical idea: instead of treating symptoms with drugs for life, deliver a one-time repair to the faulty gene itself. For the hundreds of millions worldwide living with hereditary diseases two-thirds of them children this represented more than treatment. It represented hope.
In 1992, Srivastava became the founding scientist of Avigen, the first company dedicated to AAV-based gene therapy. What began as a fragile idea slowly grew into a validated platform. The first milestone came in 2012, when Glybera was approved for lipoprotein lipase deficiency. Though it reached only 31 patients worldwide, it proved the concept: AAV gene therapy could work.
Since then, the field has flourished. Luxturna was approved to restore vision in patients with Leber congenital amaurosis.Zolgensma, using AAV9, became a breakthrough treatment for spinal muscular atrophy (SMA) a devastating childhood disease once considered fatal.
In SMA, a mutation in the SMN1 gene leads to rapid motor neuron loss. Preclinical work showed that self-complementary AAV9 (scAAV9) could cross the blood-brain barrier and restore the missing protein. In the START clinical trial, infants who would not normally live past age two received this therapy. The results were unprecedented: children gained the ability to sit, roll over, feed, and even speak. Families once preparing for loss instead witnessed milestones, they thought impossible. Behind these therapies stands decades of persistence the quiet, steady work of researchers like Srivastava who believed in AAV when few others did.
Srivastava did not stop with one success. In2017, he co-foundedLacerta Therapeutics, advancing AAV therapies for the nervous system. By 2023, he launched sAAVient Therapeutics, developing next-generation AAV3 vectors for liver diseases. And in2024, he co- founded nAAVigen Therapeutics, pioneering “nuclease-free” genome editing an approach that repairs DNA without cutting it, offering safer alternatives to CRISPR. Each venture represents not just innovation, but his philosophy: that science must keep moving forward, refining, questioning, and daring to dream.
The story of Arun Srivastava is more than a biography; it is a lesson. It shows that breakthroughs often begin as whispers faint, uncertain, and easy to dismiss. It shows that persistence, guided by intuition, can turn an impossible dream into therapies that change the lives of children and families around the world.
To young scientists: expect resistance. Expect self-doubt. Expect failure. But also expect beauty. If you carry your curiosity like a lantern, if you are willing to persist through uncertainty, your work too may one day light the way for others. Like the seed that pushes through the soil, science requires resilience. With patience and persistence, even the smallest idea can grow into discoveries that change the world.
Reference:
Ronzitti, G., Gross, D., & Mingozzi, F. (2020). Human immune responses to Adeno-
Associated virus (AAV) vectors. Frontiers in
Immunology, 11. https://doi.org/10.3389/fimmu.2020.00670Current Clinical Applications of In Vivo Gene Therapy with AAVs Mendell, Jerry R. et al.
Molecular Therapy, Volume 29, Issue 2, 464 - 488